Devices and methods for treating a vessel in a subject

ABSTRACT

A method of treating a vessel in a subject comprises the steps of advancing a device distally across a treatment zone in a vessel, wherein the device comprises an elongated catheter having a lumen and a distal end, and a radially expansive treatment element disposed in the lumen and configured for axial movement relative to the catheter; deploying the radially expansive treatment element proud of the distal end of the catheter to radially expand and circumferentially impress against the vessel lumen at a distal end of the treatment zone; and withdrawing the deployed radially expansive treatment element proximally along the treatment zone with the treatment element circumferentially impressed against the vessel lumen to mechanically and circumferentially denude the treatment zone of the vessel. The radially expansive treatment element is then recaptured into the lumen of the catheter, before the device is withdrawn from the treated vessel.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/416,838 filed on May 20, 2019, which claims priority to EuropeanApplication No. 18173170.4 filed on May 18, 2018, each of which isincorporated by reference herein in its entirety.

FIELD OF THE DISCLOSURE

The present disclosure relates to a method of treating a vessel in asubject, and a device for denuding a body lumen, in particular asuperficial vein. Also contemplated are methods for denuding a bodylumen, in particular a superficial vein, and methods of treatingvaricose veins.

BACKGROUND

Varicose veins are dilated, tortuous veins which are associated withstructural vessel wall changes, incompetent venous valves, reflux andpooling of blood. They form part of the spectrum of chronic venousdisease (CVD). Patients experience symptoms ranging from heaviness,aching pain and swelling to skin irritation, discolouration andulceration in severe cases. The cause of varicose veins is unknown butgenetic factors leading to weakness in vein wall components and valvesare important in their development.

Varicose veins occur most commonly in the superficial venous network ofthe lower limb but can also occur in pelvic and oesophageal veins incertain disease states. Superficial veins drain blood from the skin andsubcutaneous tissues into the deep venous network and ultimately back tothe heart. The primary superficial vein is the great saphenous vein(GSV) which runs from the ankle to the groin on the medial side of thelower limb. The small saphenous vein (SSV) runs from the ankle to theknee on the posterior surface of the calf. Both the GSV and SSV draininto the deep femoral vein at junctional sites in the groin andposterior to the knee respectively.

Veins contain valves to prevent backflow of blood by increasing theefficiency of muscle pumps in the leg. Valves have a bicuspid structureformed by folds of endothelium supported by connective tissue and smoothmuscle. The GSV has between 10 and 20 valves, the SSV typically hasbetween 6 and 12 valves. Incompetent valves lead to the reflux of bloodin the opposite direction to normal flow which can be seen using dopplerultrasound.

Veins have thinner walls in contrast to the thicker more elastic wallsof arteries. Veins are more compliant (flexible) allowing their lumen torange from a collapsed form in low pressure states to a distended formwhen increases in venous pressures occur. The saphenous vein wallthickness typically ranges from 200 to 700 micrometres (μm). Likearteries, the wall comprises of three primary layers: the tunica intima,media and externa. However, unlike arteries the thickness andcomposition of the layers are different resulting in more compliant,less muscular vessels. The intimal layer comprises of a single layer ofsquamous cells known as the endothelium and some thin elastic fibres,collagen and smooth muscle cells. Importantly, there is an acellularlayer of macromolecules known as the glycocalyx which covers theendothelial layer and protects it from shear forces. The glycocalyx istypically an evenly distributed structure of thickness 0.5-3 μm, whichexceeds that of the endothelial Cells (0.2 μm). The media layer iscomposed of collagen, elastic fibres and three layers of smooth musclecells. The externa or adventitia is the thickest layer and containsdense collagen, sensory nerves and elastic fibres.

Blood clotting or thrombosis can occur in both the deep and superficialvenous networks. Thrombus in superficial veins is usually self-containeddue to low-flow throughput and rarely propagates to the deep venousnetwork. It is not dangerous to the patient and does not requiretreatment unless there is associated inflammation known asthrombophlebitis. Thrombosis in the deep veins of the leg, known as deepvein thrombosis (DVT) is clinically relevant as it can cause venousoutflow obstruction, raising venous pressure and leading to oedema inthe leg. The thrombus can also travel (embolise) to the lung causing apotentially fatal condition known as pulmonary embolism (PE).

Varicose veins are the most common peripheral vascular disorder, presentin up to 40% of the adult population [1]. Risk factors include age,family history, obesity, occupations that involve long durations ofstanding and a sedentary lifestyle.

Treatment options range from conservative compression hosiery tosurgical procedures. In the USA approximately 600,000 to 700,000procedures take place per year to treat varicose veins. There thetreatment of varicose veins has transitioned from open surgery(involving stripping out of the entire GSV) to less invasive thermalendovenous catheter-based techniques (involving radiofrequency or laserenergy). Some countries including Germany and the United Kingdom, stillperform a large portion of open vein stripping procedures.

In general, catheter directed minimally invasive thermal basedtreatments are used to treat superficial venous reflux today. Asignificant limitation of using thermal energy is the need for multiplepreparation injections of high volumes of local anaesthetic mixed withsaline (tumescence) to insulate the vein and protect surrounding tissuesfrom thermal injury. This is both time-consuming for the physician andpainful for the patient due to the requirement of multiple needle stickinjections to the leg. As space is required between the skin and thevein for injection of tumescence, it also limits treatment when veinsare located close to important nerves (as is the case with treatment ofveins below the knee), near the skin or close to ulcers in patients withadvanced CVD (CEAP Classification 5 & 6).

Thermal injury to surrounding nerves and skin can still occur despitethe use of tumescent anaesthesia. The rate of nerve injury leading topersistent paresthesia is reported between 0% and 9% across a range ofstudies with higher rates for below knee GSV or SSV ablations.

Thromboembolic events are the most serious complication of superficialvenous reflux treatment. The rate of DVT and PE in real world studieshas been reported as 3% to 4% and 0.2 to 0.3% [2] respectively. Allcurrently used techniques for treatment have inherent limitations whichcan increase the risk of developing a DVT and/or PE. It is importantthat any new treatment for varicose veins aims to reduce the risk ofthromboembolic complications further.

An inherent problem with current thermal treatments is the risk ofendothermal heat induced thrombosis (EHIT) which can lead to DVT and PE.This is thought to result from forward conduction of thermal energy fromthe tip of the thermal ablation device into the deep venous system.Newer laser tip fibres emit energy radially to reduce the risk offorward conduction. However, these technologies will not prevent steambubbles spreading to adjacent non target locations which is stillconsidered a possible mechanism of action of thermal ablation inaddition to light absorption by tissues [3].

Newer non-thermal non-tumescent (NTNT) techniques for treatment of CVDhave emerged in the last 10 years. Less painful NTNT techniques are moresuitable for the clinical office setting where approximately 90% ofprocedures now take place in the US. Current NTNT techniques includechemical foam sclerotherapy, mechano-chemical ablation (MOCA) andcyanoacrylate glue (CAG) embolisation.

Chemical sclerotherapy (injection of a chemical detergent which disruptsendothelial cell membranes leading to vein occlusion by sclerosis) hasbeen used for many years but its efficacy is greatly reduced in largeveins due to the dilution effect and deactivation of sclerosant by bloodconstituents. Foaming of the sclerosant with gases to form amicro-bubble emulsion is a newer technique which displaces blood andallows the chemical to remain in contact with the endothelium forlonger. Despite this enhancement, efficacy remains significantly lowerthan thermal techniques most likely due to incomplete endothelialcoverage by the chemical sclerosant as seen in previous histologicalstudies [4]. There is also a potentially increased risk of DVT as foamcan propagate into the deep system, damaging the endothelium and forminga DVT. Higher concentrations of sclerosant foam mixtures can be moreeffective but also have a higher risk of DVT and systemic complications.Systemic complications of chemical sclerosant include transientischaemic attacks (TIAs) and even stroke due to sclerosant compoundstravelling into the arterial circulation via a small hole in the septumof the heart (patent foramen ovale). The teratogenicity of chemicalsclerosants is also unknown, contraindicating their use in pregnantwomen.

MOCA involves a combination of chemical sclerosant and a mechanicalaction from within the vein lumen to both improve distribution ofsclerosant and irritate the vein to encourage venospasm which reducesthe vein diameter. Histological studies show a limited mechanical effecton endothelial cell integrity [5]. Medium term follow up studies haveshown clinical efficacy but at levels inferior to current thermaltechniques. The distal end of current MOCA devices, which causes amechanical effect, can be prone to snagging or catching in the vein wallor valves. This results in patient discomfort, bruising, and eveninadvertent vein stripping as previously reported [6].

Glue embolization involves injection of cyanoacrylate or equivalentcompound resulting in an inflammatory response which causes veinocclusion. Limitations include the permanent implantation of a foreignmaterial in the vein lumen, subsequent risk of allergic reactions, andrisk of emboli travelling into the deep venous system causing DVT and/orPE.

Venous leg ulcers represent a major healthcare cost burden of $14Billion annually in the United States [7] and are currently primarilymanaged using compression bandages. New data arising from the EVRA study[8] announced in April 2018 provides Level I evidence to support earlyendovenous treatment of varicose veins to increase the speed of ulcerhealing in patients with CEAP class VI disease (C6). Thermal methods areless appropriate for venous ulcer patients. The need for multipleinjections of tumescent anaesthesia both lengthens the procedure for amore elderly patient population and increases the risk of infection andhaematoma formation due to the poor skin integrity adjacent to theulcer. There is also an increased risk of nerve injury resulting inparesthesia when treating veins below the knee which is often the aim oftreatment to prevent venous reflux near the ulcer bed [9].

Devices for treating blood vessels, including varicose veins, aredescribed in the following documents: WO2017194698, US2016030719,US2016030068, US2016030023, WO2016102930, US2011046543, US2016242790,JP2016034485, WO2004112569, US2017056048, GB2519057 and U.S. Pat. No.5,011,489.

U.S. Pat. No. 6,402,745 discloses a spring electrode having a helicalconfiguration that functions to electrically disrupt an inner lumen of avessel. The electrode is contained within a catheter, and a distal endof the electrode trails from the end of the catheter to contact theinner lumen of the vessel in a helical manner. This device would onlypartially denude an inner lumen of a blood vessel due to the contactarea between the electrode and the inner lumen of the vessel.

WO2014140325 describes an implantable embolization bristle device thatcan denude a blood vessel in the treatment of various indicationsincluding varicose veins and haemorrhoids. The device comprises a corewire having a multiplicity of bristles extending radially outwardly fromthe core wire, in which the bristles are configured to engage the lumenof the blood vessel to denude the vessel by brushing against the vessellumen. Bulky implantable devices are likely to cause patient discomfortin superficial veins, especially in the groin and knee areas. The use ofbristles to denude a vein results in incomplete denudation of the innerlumen of the vein. Multiple pointed and/or elongated componentssignificantly increase the risk of snagging and perforation in thincompliant vein walls.

It is an object of the present disclosure to overcome at least one ofthe above-referenced problems.

SUMMARY

The present disclosure addresses the need for a device for treatingsuperficial venous reflux, that avoids the problems associated with thethermal, chemical and glue implant treatment techniques of the prior artwhile providing comparable best in class efficacy to thermal options.These objectives are met by providing a vein denuding device comprisinga coil configured for transluminal delivery to a vein to be treatedduring the procedure (non-implant) and deployment whereby the coilcircumferentially (ideally fully circumferentially) engages an innerlumen of the vein. The coil is an oversized coil (i.e. when deployed ithas a diameter greater than the vein being treated) and has a roughenedlumen-engaging surface, so that when it is deployed the roughenedsurface bears against the inner lumen of the vein, and axial movement ofthe coil along the vein in the deployed configuration causes theabrasive surface to shear the inner lumen of the vein. This results inthe vein being mechanically denuded along a length of the vein,typically with consequent disruption of the endothelial and media layersof the vein, and ideally ultimately resulting in vein occlusion due tothe formation of a thrombus which undergoes fibrotic transformation inthe absence of an endothelial lining in a blood vessel. Ideally, theendothelium is completely circumferentially disrupted as if small areasare left intact, thrombus may not form and blood will continue to flowleading to treatment failure, recanalisation and/or early recurrence.Thus, a disclosed device may comprise a helical coil that is oversizedrelative to the diameter of the vein being treated to ensurecircumferential engagement between the roughened surface of the helicalcoil and lumen of the vein. In addition, the coil (due to itsresiliently deformable configuration) can self-adjust to allowcontinuous circumferential engagement while maintaining outward radialforce along sections of vein or vessels with varying diameters andtortuous bends (FIGS. 59A-C).

According to a first aspect of the present disclosure, there is provideda device for denuding a body lumen comprising a body lumen denuding headoperatively attached to an elongated catheter member and configured fortransluminal delivery and deployment in the body lumen, the body lumendenuding head comprising a coil that is adjustable from an uncoileddelivery configuration suitable for transluminal delivery within thecatheter member and a coiled deployed configuration having a diameterequal to or greater than the body lumen to be denuded and thatcircumferentially engages an inner lumen of the body lumen, whereby thecoil has an abrasive surface configured to denude the body lumen whenthe helical coil is moved axially with or without rotation along thebody lumen in the coiled configuration.

According to a second aspect of the present disclosure, there isprovided a method of denuding a body lumen that employs a devicecomprising a body lumen denuding head operatively attached to anelongated catheter member and configured for transluminal delivery anddeployment in a body lumen, the method comprising the steps of:

transluminally delivering the body lumen denuding head to a body lumento be treated;

deploying the body lumen denuding head within the body lumen to betreated, in which the body lumen denuding head has an abrasive surfacein circumferential contact with an inner lumen of the body lumen whendeployed;

moving the body lumen denuding head along the section of the body lumento be treated with the abrasive surface in circumferential contact withthe body lumen, whereby the abrasive surface denudes the body lumen;

recapturing the denuding head into the catheter member; and

removal of the device from the body lumen.

In one embodiment, the coil is a helical coil.

In one embodiment, the coil is “oversized” with respect to the diameterof the body lumen to be treated.

In one embodiment, the diameter of the coil (or the maximum diameter inthe case of helical coils whose diameter varies along its length) isgenerally at least about 5% greater than the diameter of the body lumento be treated (or in the case of body lumens with varying diameter, atleast about 5% greater than the diameter of the body lumen at it widestpoint), for example at least 10%, 15%, 20%, 25% or 30% greater than thediameter of the body lumen to be treated, and typically from 5-30%greater. It is important that the coil is oversized along at least oneturn of the coil, and typically oversized along 1-2 turns.

In one embodiment, the device is configured to denude an internal lumenof a vein.

In one embodiment, the coil comprises a shape memory material and isconfigured to adopt the coiled configuration when deployed.

The helical coil is generally sufficiently resiliently deformable toself-adjust to maintain a circumferential radial force against the wallof a body lumen of varying diameter as it travels along the body lumen.In one embodiment, the helical coil is configured to reflexivelyself-adjust its diameter in response to variable vein diameters andvariable axial forces during axial movement along the treatment zonewhile maintaining an outward radial force on the vein.

The helical coil in its deployed state is oversized with respect to thewidest part of the body lumen (or the section of the body lumen to betreated), thereby exerting a radial force around the full circumferenceof the body lumen along the length of the body lumen to be treatedincluding its widest point.

The helical coil is typically sufficiently resiliently deformable toallow the coil pass around tortuous bends in the body lumen, whilemaintaining a radial force against the body lumen along the bend.

The helical coil is typically sufficiently resiliently deformable toallow the coil pass through a narrowing or obstruction in a body lumen,for example a valve in a vein.

In one embodiment, the device comprises an elongated control arm for thebody lumen denuding head disposed within the catheter member.

Typically, the control arm is connected to a proximal end of the coil.

The control arm may be a hypotube, for example a hypotube formed fromstainless steel, polymer or another material.

In one embodiment, the coil has a single coil element.

In one embodiment, the single coil element has 1-5, 1-4 turns, 1-3turns, and preferably 1-2 turns, and ideally about 1.5 to 1.7 turns, ina deployed configuration.

In one embodiment, the diameter of the helical coil varies along itslength.

In one embodiment, the diameter of the helical coil increases towardsone end (i.e. conical).

The increase in diameter may be proximal to distal, or distal toproximal.

As used herein, the term “proximal” as applied to a helical coil refersto an end of the device that is closest to the introduction point—theterm “distal” should be construed accordingly.

In one embodiment, the diameter of the helical coil increases towards amid-point along the coil, and then decreases.

In one embodiment, the distal end of the coil terminates at a pointdisposed along, or adjacent to, a longitudinal axis of the helical coil.

In one embodiment, the helical coil has a proximal section of a firstdiameter, an intermediate section of reduced diameter relative to theproximal section, and a distal section of increased diameter relative tothe intermediate section.

In one embodiment, the helical coil has a proximal and distal helicalcoil section, and an intermediate connecting (transition) section thatis typically not helical and may be straight or curved.

In one embodiment, one of the proximal or distal helical coil sectionsis a right-handed helix, and the other of the proximal or distal helicalcoil sections is a left-handed helix.

In one embodiment, the proximal helical coil section is a right-handedhelix and distal helical coil section is a left-handed helix.

In one embodiment, the distal helical coil section is a right-handedhelix and proximal helical coil section is a left-handed helix.

In one embodiment, the coil comprises a plurality of coil elements, forexample 2, 3, 4, 5 or more. Typically, each coil element is helical.

The helical coils may be arranged in a double, triple or quadruple coilarrangement.

Typically, the coil elements are co-axial.

Typically, each coil element has the same diameter when deployed.

Typically, each coil element has the same pitch when deployed. When in adeployed configuration, the plurality of coil elements together providecircumferential engagement of the inner lumen of the body lumen. Thus,each coil element may be configured such that, in a deployedconfiguration, it engages only a part of the circumference of the innerlumen, for example 90°-270°, 90°-180°, 180°-270° of engagement with thecircumference of the body lumen.

The coil elements may be connected to the same control arm.

In one embodiment, the coil has two helical coil elements, for example adouble helix.

Typically, each of the two helical coil elements has at least 0.5 turnswhen deployed, and typically from 0.5 to 1.0 turns or 0.5 to 0.7 turns.

In one embodiment, the coil has three helical coil elements, for examplea triple helix.

Typically, each of the three helical coil elements has at least 0.3turns when deployed, and typically from 0.3 to 1.0 turns or about 0.3 to0.5 turns, when deployed.

In one embodiment, the coil has four helical coil elements.

Typically, each of the four helical coil elements has at least 0.25turns when deployed, and typically from 0.25 to 0.75 turns whendeployed.

In one embodiment, the plurality of coil elements are connected togetherat their distal ends.

In one embodiment, the plurality of coil elements are unconnected attheir distal ends.

In one embodiment, the coil or each coil element is helical and isconfigured to have a pitch of about 0.5 to 1.5 times the coil diameterin the coiled configuration when deployed.

In one embodiment, the coil or each coil element is helical and isconfigured to have a pitch approximately equal to the diameter in thecoiled configuration when deployed.

In one embodiment, one of the helical coil elements is axially spacedfrom another coil element. Generally, in this embodiment, the controlarm (generally a distal end of the control arm) is bifurcated to providedistal control arms, each connected to one of the helical coils.However, the device may comprise separate control arms, for independentcontrol of the two helical coils.

In an embodiment of the vein denuding head having axially spaced aparthelical coils, the control arm of the distal helical coil typicallypasses axially through the proximal helical coil (through one, more orall of the coils making up the proximal helical coil).

In one embodiment, the proximal helical coil has a maximum diameter thatis greater than the maximum diameter of the distal helical coil (forexample, 1.5-4 times greater).

In another embodiment, the proximal helical coil has a maximum diameterthat is less than the maximum diameter of the distal helical coil (forexample 1.5 to 4 times less).

In one embodiment, the pitch of the proximal and distal coil elements isdifferent.

In one embodiment, the narrower coil has a greater pitch.

In one embodiment, the distal and/or proximal helical coil is conical.

In one embodiment, the distal and proximal helical coils are conical.

Typically, the diameter of the helical coil increases in the proximaldirection (i.e. towards the entry point of the device).

In one embodiment, the coil or each coil is configured to have adiameter in the coiled configuration when deployed that is at leastequal to or greater than the diameter of the vein to be treated.

In one embodiment, the or each helical coil is conical (i.e. thediameter of the coil increases or decreases as it approaches the deviceentry point—i.e. proximally).

Typically, the diameter of the helical coil increases in the proximaldirection.

In one embodiment, the coil has a profile selected from circular, oval,curved, convex, concave, T-shaped, inverted T-shaped, or any othershape.

In one embodiment, the coil has a flat internal surface, and an externalsurface that is curved, concave, convex, or inverted T-shaped. Helicalcoils having these profiles are illustrated in FIGS. 34A to 41B.

In one embodiment, the roughened surface of the coil or each coilelement is formed by treating the surface of the coil, typically anexternal body lumen facing surface of the coil (and/or a lateral surfaceof the coil), to introduce surface roughness.

In one embodiment, an internal surface of the coil is not roughened, andideally smooth. This facilitates retraction of the coil into thecatheter member where the smooth surface of the coil comes into contactwith the mouth of the catheter.

In one embodiment, surface roughness is produced by mechanical,electrical, chemical abrasion, or abrasion by other means.

In one embodiment, the external surface of the coil comprisesindentations configured to provide the roughened surface.

In one embodiment, the indentations are configured to provide teeth onthe surface. In one embodiment, the indentations are transverseindentations.

In one embodiment, the transverse indentations extend fully across theexternal surface of the coil.

In one embodiment, the transverse indentations are disposed on each sideof the external surface (i.e. when the external surface of the coil isconcave).

In one embodiment, the indentations are longitudinal, and extend fullyor at least partially along the length of the helical coil. Thelongitudinal indentations may be straight, curved, wavy, zig-zagged,diamond shaped or any configuration.

In one embodiment, the helical coil has an inverted T-shape profile, inwhich the teeth from the leg of the inverted T shape.

In one embodiment, the teeth have a profile selected from triangular,polygonal, rhomboid or any other profile configured to scrape away anendothelial layer of a body lumen.

In one embodiment, the coil comprises lateral teeth.

In one embodiment, the coil has a flat internal and external surface,and lateral teeth.

In one embodiment, the coil is formed from a flat wire with a diamondtextured and roughened outer surface and a smooth inner surface.

In one embodiment, the coil has grooves or pores to act as reservoirsfor therapeutic agents.

In one embodiment, the coil or each coil element comprises a core wireand the abrasive surface is formed by a second wire wound helicallyaround the core wire to form a second coil.

In one embodiment, the second wire has a polygonal cross-section.

In one embodiment, the second coil has a pitch of 1 to 5 mm.

In one embodiment, a pitch of the second coil is greater at a proximalend thereof.

In one embodiment, a pitch of the second coil is lesser at a proximalend thereof.

In one embodiment, the second coil is bonded to the core wire, typicallyat a plurality of locations.

In one embodiment, a surface of the second wire is treated to introducesurface roughness.

In one embodiment, the helical coil has a proximal section that isgenerally co-axial with a longitudinal axis of the helical coil.

In one embodiment, the helical coil has a distal section that isgenerally co-axial with a longitudinal axis of the helical coil.

In one embodiment, the control arm for the body lumen denuding head isdisposed within the catheter member. Typically, the control arm isconnected to a proximal end of the coil. The control arm may be ahypotube, for example a hypotube formed from stainless steel, polymer oranother material.

In one embodiment, the control arm is configured for axial movement todeploy the body lumen denuding head at a target location in a body, andwithdraw the body lumen denuding head into the catheter member aftertreatment.

In one embodiment, the control arm is configured for rotational movementto rotate the body lumen denuding head in the body lumen.

In one embodiment, the device comprises a distal control arm connectedto a distal end of the coil and a proximal control arm connected to aproximal end of the coil, whereby relative axial movement of the distaland proximal arms effects coiling and uncoiling of the coil.

In one embodiment, a distal end of the coil comprises an atraumatichead, for example a flexible material or a spherical ball.

In one embodiment, the device comprises a handle operatively connectedto a proximal end of the catheter member and configured to control thedeployment and retraction of the coil. In one embodiment, the handlecomprises a control element configured for axial adjustment of thecontrol arm or arms with or without rotation. In one embodiment, thehandle comprises a control element configured for rotational adjustmentof the control arm or arms.

In one embodiment, the device is configured for adjustment between: adelivery configuration in which the helical coil is stowed within thecatheter member in an uncoiled configuration,

a first body lumen denuding configuration in which in use the coil isdeployed in the body lumen to be treated at a first axial position andbears against a circumference of the body lumen;

a second body denuding configuration in which in use the coil isdeployed in the body lumen to be treated proximal to the first axialposition and bears against a circumference of the body lumen; and

a withdrawal configuration in which the coil is stowed within thecatheter member.

The method of the disclosure may be employed to venous disease,especially superficial venous reflux, and preferably varicose veins. Theveins treated are generally saphenous veins, and typically the GreatSaphenous Vein (GSV) or Small Saphenous Vein SSV). In one embodiment ofthe method of the disclosure, the body lumen denuding head is movedproximally towards the access site along the section of the body lumento be treated.

In one embodiment, the method comprises treating a section of the bodylumen having a length of at least 2, 4, 6, 8, 10, 12, 14, 16, 18 or 20cm.

In one embodiment, the method is for completely occluding a body lumen,for example a vein or an artery.

In one embodiment, the method is for partially occluding a body lumen,for example a vein or an artery. Thus, the device and method may beemployed to treat conditions or indications characterised bydysregulated or unwanted blood volume or flow rate through a section ofthe vasculature, by employing the device to partially occlude thesection of the vasculature.

In another case, the method is to thicken the wall of a vein by inducingsignificant wall thickening such as circumferential intimal hyperplasia.This effect “arterialises” a vein making it more resilient to the effectof higher blood pressure and shear forces. This thickening effect shouldbe self-limiting when it occurs in response to a once off mechanicalstimulus as opposed to the uncontrolled intimal hyperplasia that occurswhen veins are exposed to persistently higher shear forces when used asconduits in the arterial system. Thus, the device and method may beemployed to prepare a vein prior to grafting into the arterialcirculatory system.

The body lumen may be vasculature, for example an artery or vein.

In one embodiment, the method is a method of treating a varicose vein bydenuding a section of the superior rectal artery.

In one embodiment, the method is a method of treating haemorrhoids bydenuding a section of the vein.

In one embodiment, the method is a method of thrombectomy by denuding asection of a vein or artery occluded by thrombus.

In one embodiment, the method is as a preparation step to prime a targetarea of a body lumen (i.e. section of vasculature) prior to theimplantation of a medical device such as a valve or stent.

In one embodiment, the method is as a preparation step to prime a targetarea of an artery prior to grafting to reduce risk of Type 1 endoleaks.

In one embodiment, the body lumen being denuded is an artery feeding atumour such as a solid tumour.

In one embodiment, the body lumen is a portal vein providing nutrientsfrom the intestine to the liver. In one embodiment, the subject beingtreated has a liver disease such as cancer and the method is typicallyperformed prior to liver resection.

In one embodiment, the body lumen being treated is a blood vesselforming part of an arteriovenous malformation.

In one embodiment, the body lumen being treated is a spermatic vein.Thus, methods of treating varicocele are also described.

In one embodiment, the body lumen being treated is a blood vessel (i.e.uterine artery) supplying a uterine fibroid.

In one embodiment, the body lumen being treated is part of thegastro-intesinal tract such as the duodenum, jejunum, or ileum.

In one embodiment, the body lumen being treated is the prostatic artery.

In one embodiment, the body lumen being treated is a pelvic vein.

In one embodiment, the method is employed to treat Patent Foramen Ovale(PFO), by denuding a contacting surface of the arterial septal flapsinvolved in PFO.

In one embodiment, the method is employed to treat Patent DuctusArteriosus, by disrupting mucosal layers of the ileocaecal valve andileum.

In one embodiment, the method is employed to treat Small Intestinal;Bacterial Overgrowth, by denuding the ductus arteriosus.

In one embodiment, the method is employed to treat Barrett's Oesophagus,by mechanically ablating or denuding cells (abnormal cells) in the loweroesophagus.

In one embodiment of the method, the method includes a step ofdelivering a liquid sclerosant into the body lumen distal of thecatheter member.

In one embodiment of the method, the method includes a step ofdelivering thermal energy to the body lumen by conduction through thelumen engaging surface of the device.

In one embodiment of the method, the method includes a step of using anintravenous ultrasound (IVUS) probe attached or incorporated in denudinghead element to determine the vessel response to treatment.

In one embodiment of the method, therapeutic agents coat the outersurface or are embedded in grooves or pores on the device and deliveredto the inner surface of a body lumen.

In one embodiment of the method, the method employs a body lumendenuding device.

In another aspect, the present disclosure provides a method of treatinga vessel (or any body lumen) in a subject, comprising the steps of:

-   -   advancing a device distally across a treatment zone in the        vessel, wherein the device comprises an elongated catheter        having a lumen and a distal end, and a radially expansive        treatment element disposed in the lumen and configured for axial        movement relative to the catheter;    -   deploying the radially expansive treatment element proud of the        distal end of the catheter to radially expand and        circumferentially impress against the lumen at a distal end of        the treatment zone;    -   withdrawing the deployed radially expansive treatment element        proximally along the treatment zone with the treatment element        circumferentially impressed against the vessel lumen to        mechanically and circumferentially denude the treatment zone of        the vessel;    -   recapturing the radially expansive treatment element into the        lumen of the catheter; and    -   withdrawing the device from the treated vessel.

In one embodiment, the vessel is a varicose vein, and in which themethod is typically a method of treating the varicose vein by denuding alumen of the vein to cause occlusion of the varicose vein.

In one embodiment, the step of mechanically and circumferentiallydenuding the treatment zone of the vessel comprises affectingcircumferential exposure of the subendothelial vessel surface along thetreatment zone.

In one embodiment, the radially expansible treatment element isself-adjustable from an undeployed delivery configuration suitable fortransluminal delivery within the catheter and a deployed radiallyexpanded configuration having a diameter greater than the vessel in thetreatment zone.

In one embodiment, the radially expansible treatment element isresiliently deformable, wherein the radially expansible treatmentelement reflexively self-adjusts its diameter in response to variablevessel diameters and variable axial forces during axial movement alongthe treatment zone while maintaining an outward radial force on thevessel.

In one embodiment, an external vessel-lumen facing surface of theradially expansible treatment element has a roughened surface.

In one embodiment, an external vessel-lumen facing surface of theradially expansible treatment element has a roughened surface, in whichthe roughened surface comprises a macro and micro abrasive surface.

In one embodiment, the vessel is a superficial vein such as the greatsaphenous vein, the small saphenous vein, a perforator vein or tributaryvein.

In one embodiment, the superficial vessel is a vein selected from thegreat saphenous vein and the short saphenous vein.

In one embodiment, the method is a method of treatment of superficialvenous reflux in a subject, and in which the vessel is a superficialvein.

In one embodiment, the method is a method of treatment of a varicosevein in the subject, wherein the vein being treated is varicose.

In one embodiment, the method results in occlusion of the treatedvessel.

In one embodiment, the method is a method of narrowing but not occludinga vessel.

In one embodiment, the step of withdrawing the deployed radiallyexpansive treatment element proximally along the treatment zone causesmechanical stretch or the vessel wall resulting in activation of smoothmuscle within the wall leading to vasospasm along the treatment zone andoptionally prevention of nitric oxide secretion from endothelial cellsand subsequent prolongation of vasospasm.

In one embodiment, the radially expansible treatment element is a coil.

In one embodiment, the radially expansible treatment element is ahelical coil.

In one embodiment, the method is performed using an imaging modalitysuch as ultrasound guidance.

In one embodiment, the method includes the step of recapturing thetreatment element into the catheter member comprises returning thetreatment element to an undeployed state, allowing repositioning andrepeat deployment.

In one embodiment, the method includes a step of deploying a temporarylumen occluding element during at least one of the steps to halt bloodflow in high flow vessels.

In another aspect, the present disclosure provides a method of treatingsuperficial venous reflux in a superficial vein in a subject comprisinga step of mechanically and circumferentially denuding a treatment zoneof the superficial vein.

In one embodiment, the treatment zone of the superficial vein that iscircumferentially denuded has a length of 5 to 25 cm.

In one embodiment, the step of mechanically and circumferentiallydenuding the treatment zone of the superficial vein comprises effectingcircumferential exposure of the subendothelial vessel surface along thetreatment zone.

In one embodiment, the step of mechanically and circumferentiallydenuding the treatment zone of the vein comprises deploying a veindenuding device in a distal part of the target section of thesuperficial vein to circumferentially impress against the vein lumen,and withdrawing the deployed vein denuding device proximally along thetreatment zone with the device circumferentially impressed against thevein lumen.

In one embodiment, the step of mechanically and circumferentiallydenuding the treatment zone of the vessel comprises effectingcircumferential exposure of the subendothelial vessel surface along thetreatment zone.

In one embodiment, the vein denuding device is self-adjustable from anundeployed delivery configuration suitable for transluminal deliverywithin the catheter and a deployed radially expanded configurationhaving a diameter greater than the vessel in the treatment zone.

In one embodiment, the vein denuding device is resiliently deformable,wherein the radially expansible treatment element reflexivelyself-adjusts its diameter in response to variable vessel diameters andvariable axial forces during axial movement along the treatment zonewhile maintaining an outward radial force on the vessel.

In one embodiment, an external vessel-lumen facing surface of the veindenuding device has a roughened surface.

In one embodiment, an external vessel-lumen facing surface of the veindenuding device has a roughened surface, in which the roughened surfacecomprises a macro and micro abrasive surface.

In one embodiment, the radially expansible treatment element is a coiland preferably a resiliently deformable coil.

In one embodiment, the radially expansible treatment element is aresiliently deformable helical coil.

In one embodiment, the method is performed under ultrasound guidance.

In one embodiment, the axial movement of the radially expansivetreatment element (or helical coil) is automatic or semi-automaticallycontrolled independent of the operator.

In one embodiment, the device is configured to collect data for operatorfeedback, or for further interpretation by human, statistical, big-dataor machine learning analysis. This, the device may incorporate one ormore sensors configured to detect in-vivo data, for example temperature,pressure, electrical impedance or the like, of tissue or blood. Thedevice may be configured to relay the in-vivo data wirelessly or alongwires disposed in the catheter member. The device may be configured torelay data to a remote processor.

Other aspects and preferred embodiments of the disclosure are definedand described in the other claims set out below.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is an illustration of the human vasculature in an axial planeshowing the composition of a typical vein wall including the innerlining of the vein (tunica intima) with associated endothelium andglycocalyx coverings, adjacent intermediate layer (tunica media) andouter layer (tunica adventitia). The typical thickness in micrometresfor an adult vein wall is also included.

FIG. 2 is a histological axial section of a caprine vein 28 days postmechanical endovenous treatment in our animal study. The imagehighlights the importance of circumferential coverage in terms ofendothelial cell destruction. It is taken from a partially treated veinin our animal study. The upper right corner shows a clot adherent to thevein wall with inflammatory cell migration into the thrombus from theouter layers in the early phases of fibrotic transformation. The lowerleft corner has intact endothelium remaining. Thrombus has failed toadhere or has recanalised due to the effect of the intact endothelium.Blood can flow in the channel leading to overall treatment failure inthis segment.

FIG. 3 shows a histological axial section of a goat vein at 28 days postmechanical endovenous treatment in our animal study. Circumferentialdenudation of the endothelium and shearing due to frictional forcesbetween superficial and deep layers has occurred. The lumen is filledwith adherent thrombus undergoing fibrotic change as it is invaded byinflammatory cells including collagen forming fibroblasts.

FIG. 4 illustrates a device for denuding a body lumen according to afirst embodiment of the disclosure.

FIG. 5 is a side elevational view of the device of FIG. 1.

FIG. 6 is a perspective view of the device of FIG. 1.

FIG. 7 is a distal end elevational view of the device of FIG. 1

FIG. 8 is a detailed view of a section of the helical coil of the deviceof FIG. 4, showing the serrated surface formed by the second wirehelically wound around the core wire.

FIG. 9 is a detailed view of a distal end of the helical coil of thedevice of FIG. 4, showing the higher pitch of the second wire and thespherical end-hub.

FIG. 10 is a detailed view of a proximal end of the helical coil of thedevice of FIG. 4, showing the helical coil attached to a steel hypotube,which is mounted within the catheter member.

FIG. 11 is a detailed view of a proximal end of the helical coil of thedevice of FIG. 4, showing the shorter pitch of the second wire as itapproaches the proximal end of the coil to aid recapture.

FIG. 12 is a perspective view of a helical coil forming part of a deviceaccording to an alternative embodiment of the disclosure, in which alumen-engaging surface of the second wire incorporates a series ofhelical indentations.

FIG. 13 is a side elevational view of the device of FIG. 4 in a veinwith the helical coil in a deployed configuration. This figureillustrates how the oversized coil is forced into circumferentialengagement with the body lumen, and that the radial force exerted by theoversized coil deforms the vein.

FIG. 14 is a similar illustration to FIG. 13, and shows how a smallerdiameter coil is employed with a smaller diameter vein.

FIG. 15 is a perspective view of the device deployed in a view outsidethe vein, showing how the radial forces exerted by the deployed coildeform the vein.

FIG. 16 is a detailed view of the abrasive surface of the helical coilengaging the inner lumen of a vein.

FIG. 17 illustrates the procedure of endovenous mechanical denudation ofa lower limb vein to cause occlusion and prevent reflux in the treatmentof superficial venous disease. The undeployed device within the outercatheter is shown near the Sapheno-femoral junction following ultrasoundguided navigation.

FIG. 18 illustrates the deployed radially expansive coil duringtreatment causing vasospasm of the treated section.

FIG. 19 illustrates recapture of the radially expansive element prior towithdrawal of the catheter.

FIG. 20 is a perspective view of a device for denuding a body lumenaccording to a further embodiment of the disclosure.

FIG. 21 is an end view of the device of FIG. 20.

FIG. 22 is a side elevational view of the device of FIG. 20 in apartially deployed configuration.

FIG. 23 is a side elevational view of the device of FIG. 20 in a fullydeployed configuration.

FIG. 24 is another side elevational view of the device of FIG. 20 in afully deployed configuration.

FIG. 25 illustrates a device for denuding a body lumen according to afurther embodiment of the disclosure, in which the coil is made up oftwo co-axial helical coil elements.

FIG. 26 is an end view of the device of FIG. 25.

FIG. 27 is a side elevational view of the device of FIG. 25.

FIG. 28 illustrates a device for denuding a body lumen according to afurther embodiment of the disclosure, in which the coil is made up offour co-axial helical coil elements.

FIG. 29 is an end view of the device of FIG. 28.

FIG. 30 is a side elevational view of the device of FIG. 28.

FIG. 31 illustrates a device for denuding a body lumen according to afurther embodiment of the disclosure, in which the coil is made up offour co-axial helical coil elements which are joined at their distalends.

FIG. 32 is an end view of the device of FIG. 31.

FIG. 33 is a side elevational view of the device of FIG. 31.

FIG. 34A and FIG. 34B are perspective and side elevational views of asection of a helical coil according to the disclosure.

FIG. 35A and FIG. 35B are perspective and side elevational views of asection of a further helical coil according to the disclosure.

FIG. 36A and FIG. 36B are perspective and side elevational views of asection of a further helical coil according to the disclosure.

FIG. 37A and FIG. 37B are perspective and side elevational views of asection of a further helical coil according to the disclosure.

FIG. 38A and FIG. 38B are perspective and side elevational views of asection of a further helical coil according to the disclosure.

FIG. 39A and FIG. 39B are perspective and side elevational views of asection of a further helical coil according to the disclosure.

FIG. 40A and FIG. 40B are perspective and side elevational views of asection of a further helical coil according to the disclosure.

FIG. 41A and FIG. 41B are perspective and end elevational views of asection of a further helical coil according to the disclosure.

FIG. 42A and FIG. 42B are side elevational and perspective views of afurther embodiment of a helical coil forming part of device according tothe disclosure.

FIG. 43A and FIG. 43B are side elevational and perspective views of afurther embodiment of a helical coil forming part of device according tothe disclosure.

FIG. 44A and FIG. 44B are side elevational and perspective views of afurther embodiment of a helical coil forming part of device according tothe disclosure.

FIG. 45A and FIG. 45B are side elevational and perspective views of afurther embodiment of a helical coil forming part of device according tothe disclosure.

FIG. 46A and FIG. 46B are perspective and side elevational views of afurther embodiment of a helical coil forming part of device according tothe disclosure.

FIG. 47A and FIG. 47B are perspective and side elevational views of afurther embodiment of a helical coil forming part of device according tothe disclosure.

FIGS. 48A to 48C are side elevational views, and a perspective view, ofa further embodiment of a helical coil forming part of device accordingto the disclosure.

FIG. 49A and FIG. 49B are side elevational and perspective views of avein-denuding head forming part of a device according to the disclosure,having two axially spaced-apart helical coils.

FIG. 50A and FIG. 50B are side elevational and perspective views of avein-denuding head forming part of a further device according to thedisclosure, having two axially spaced-apart helical coils.

FIG. 51A is a perspective view of a vein-denuding head forming part of afurther device according to the disclosure, having two axiallyspaced-apart helical coils.

FIG. 52A illustrates small arteries feeding a tumor, and FIG. 52B is anexploded view of part of one of the arteries showing a device of thepresent disclosure in use to denude a section of the lumen of the arteryand occluding the artery due to the formation of thrombus.

FIG. 53A illustrates portal vein vasculature, and FIG. 53B is anexploded view of part of one of the veins showing a device of thepresent disclosure in use to denude a section of the lumen of the arteryand occluding the artery due to the formation of thrombus.

FIG. 54 illustrates a natural arteriovenous shunt section of vasculatureincorporating a malformation, and a device according to the presentdisclosure in use denuding a section of the shunt to occlude themalformed shunt by formation of a thrombus.

FIG. 55 illustrates the left spermatic vein and varicoceles surroundingthe left testicle, and a device according to the present disclosure inuse denuding a section of the left spermatic vein to occlude the vein byformation of a thrombus.

FIGS. 56A to 56C illustrate how the helical coil forming part of adevice of the present disclosure can self-adapt to varying vesseldiameter, and constrictions or narrowed sections in vessels, as it ispulled through the vessel: (A) the deployed helical coil incircumferential contact with the lumen of the vessel approaching thenarrowed section of the vessel; (B) the helical coil having passedthrough the narrowed section and maintaining circumferential contactwith the lumen of the vessel just proximal of the narrowed section; and(C) the helical coil moving proximally of the narrowed section andself-adjusting to maintain circumferential contact with the lumen of thevessel.

FIGS. 57A to 57C illustrate how the helical coil forming part of adevice of the present disclosure can navigate through valves in veins asit is pulled through a section of a vein: (A) the deployed helical coilin circumferential contact with the lumen of the vein distal of thevalve; (B) the helical coil passing through the valve without snagging;and (C) the helical coil moving proximally of the narrowed section andself-adjusting to maintain circumferential contact with the lumen of thevessel.

FIG. 58A and FIG. 58B illustrate how the helical coil forming part of adevice of the present disclosure can navigate through a section ofvasculature that progressively narrows and self-adjusts the diameter ofthe coil to maintain circumferential engagement with the lumen of thevessel: (A) the deployed helical coil in circumferential contact with awide section of the vessel; (B) the deployed helical coil incircumferential contact with a narrower section of the vessel;

FIGS. 59A to 59C illustrate how the helical coil forming part of adevice of the present disclosure can self-adapt to varying vesseldiameter and navigate a tortuous vessel: (A) the deployed helical coilin circumferential contact with the lumen of the vessel at a narrowedsection of the vessel; (B) the helical coil navigating through a sharpturn in the vessel while maintaining circumferential contact with thelumen of the vessel; and (C) the helical coil navigating through a sharpturn in the vessel of greater diameter while maintaining circumferentialcontact with the lumen of the vessel.

FIGS. 60A to 60C illustrate how the helical coil forming part of adevice of the present disclosure can self-adjust the diameter of thecoil to maintain circumferential engagement with the lumen of the vesselwhen the vessel actively constricts due to vasospasm or tapers to asmaller width: (A) the deployed helical coil in circumferential contactwith a vessel section of length I and diameter D prior to vasospasm ofthe vessel; (B) Section A-A is an axial view of the helical wire incontact with the vessel wall under a hoop force HF generated by pressurefrom a constraint force P; (C) the deployed helical coil incircumferential contact over an extended length L within the constrictedvessel of diameter d during vasospasm.

FIGS. 61A to 61C illustrate the static force variables on the deployedcoil as it comes under an axial Force FA; (A) prior to movement at thebeginning of withdrawal in a vessel of diameter D with contact force ofthe coil outwards FC and constraint force of the vessel P; (B)lengthened to a length of L in a narrowed vessel of diameter d; (C) In asignificantly narrowed vessel of diameter e with the coil lengthened toS. There is loss of vessel wall contact over proximal section of coil toreduce static friction and allow atraumatic passage of the coil.

FIG. 62A and FIG. 62B illustrate how a device of the present disclosurecan be used to treat vasculature having abnormally high blood volumes orhigh blood flow rates, to partially occlude the vessel to normalise theblood volume or flow: (A) shows a pulmonary artery prior to treatment,with the device deployed in the artery and being pulled proximally; (B)shows the chronic changes in the pulmonary artery of FIG. 62A aftertreatment with the device with intimal hyperplasia partially occluding(narrowing) the artery to provide for reduced blood volume and flowthrough the artery.

FIG. 63 illustrates an oblique view of an embodiment with a flattenedwire having a smooth inner surface and roughened outer surface with adiamond pattern in a typical vessel.

FIGS. 64A to 64D illustrate an oblique view of the device within thevessel. Close-up views of the outer texturing embodiments show (B) amacro-abrasive grooved surface that is perpendicular to the vein wall inthe direction of withdrawal; (C) a macro-abrasive surface that isparallel to the vein wall in the direction of withdrawal; (D) a diamondconfiguration of a macro-abrasive surface.

FIG. 65 illustrates the tip of a modified intravenous cannula modifiedto store a miniaturised helical coil in an undeployed state.

FIG. 66A and FIG. 66B illustrate the use of a modified cannula as shownin FIG. 65, to access a target vein and deploy a helical coil followingwithdrawal of the outer sheath.

FIG. 67 illustrates the access of superficial leg tributary veins withthe cannula device of FIG. 65.

FIGS. 68A to 68D illustrate a method of deploying a miniaturised coil intributary veins. (A) Intravenous access with a guidewire is achieved anda sheath is inserted over the guidewire; (B) The sheath is advanced inthe vein and the guidewire is removed; (C) The sheat is withdrawn toexpose the stored helical abrasive coil element; (D) The sheath and coilare withdrawn together to treat the vein section.

FIG. 69A and 69B illustrate the sheath used in FIGS. 68A-68D which holdsan undeployed helical coil in its internal perimeter to accommodatepassage of a guidewire.

FIG. 70A and 70B illustrate a method using a peel away introducer sheathto deploy a helical coil in a target vein.

FIG. 71 illustrates the use of a helical ablation coil to treat pelvicvein reflux in the left ovarian vein.

FIGS. 72A to 72C illustrate vein remodelling in Arterio-fistulaformation (A) Normal vein; (B) Intimal hyperplasia with self limitedthickening of the intimal layer. (C) Vein graft failure due to excessiveintimal hyperplasia causing lumen obstruction.

FIG. 73 illustrates the use of helical coil with roughened inner surfaceand smooth outer surface to remove an adherent thrombus in a bloodvessel.

FIG. 74A and FIG. 74B illustrate the use of a helical coil with apartially textured outer surface allowing selective treatment of avessel wall with or without rotational force in addition to axialwithdrawal

FIG. 75 illustrates the use of a helical coil during an endoscopyprocedure to resurface the mucosal layer of the duodenum in thetreatment of diabetes.

DETAILED DESCRIPTION

All publications, patents, patent applications and other referencesmentioned herein are hereby incorporated by reference in theirentireties for all purposes as if each individual publication, patent orpatent application were specifically and individually indicated to beincorporated by reference and the content thereof recited in full.

Definitions and General Preferences

Where used herein and unless specifically indicated otherwise, thefollowing terms are intended to have the following meanings in additionto any broader (or narrower) meanings the terms might enjoy in the art:

Unless otherwise required by context, the use herein of the singular isto be read to include the plural and vice versa. The term “a” or “an”used in relation to an entity is to be read to refer to one or more ofthat entity. As such, the terms “a” (or “an”), “one or more,” and “atleast one” are used interchangeably herein.

As used herein, the term “comprise,” or variations thereof such as“comprises” or “comprising,” are to be read to indicate the inclusion ofany recited integer (e.g. a feature, element, characteristic, property,method/process step or limitation) or group of integers (e.g. features,elements, characteristics, properties, method/process steps orlimitations) but not the exclusion of any other integer or group ofintegers. Thus, as used herein the term “comprising” is inclusive oropen-ended and does not exclude additional, unrecited integers ormethod/process steps.

As used herein, the term “disease” is used to define any abnormalcondition that impairs physiological function and is associated withspecific symptoms. The term is used broadly to encompass any disorder,illness, abnormality, pathology, sickness, condition or syndrome inwhich physiological function is impaired irrespective of the nature ofthe aetiology (or indeed whether the aetiological basis for the diseaseis established). It therefore encompasses conditions arising frominfection, trauma, injury, surgery, radiological ablation, poisoning ornutritional deficiencies.

As used herein, the term “treatment” or “treating” refers to anintervention (e.g. the administration of an agent to a subject) whichcures, ameliorates or lessens the symptoms of a disease or removes (orlessens the impact of) its cause(s) (for example, the reduction inaccumulation of pathological levels of lysosomal enzymes). In this case,the term is used synonymously with the term “therapy”.

Additionally, the terms “treatment” or “treating” refers to anintervention (e.g. the administration of an agent to a subject) whichprevents or delays the onset or progression of a disease or reduces (oreradicates) its incidence within a treated population. In this case, theterm treatment is used synonymously with the term “prophylaxis”.

As used herein, an effective amount or a therapeutically effectiveamount of an agent defines an amount that can be administered to asubject without excessive toxicity, irritation, allergic response, orother problem or complication, commensurate with a reasonablebenefit/risk ratio, but one that is sufficient to provide the desiredeffect, e.g. the treatment or prophylaxis manifested by a permanent ortemporary improvement in the subject's condition. The amount will varyfrom subject to subject, depending on the age and general condition ofthe individual, mode of administration and other factors. Thus, while itis not possible to specify an exact effective amount, those skilled inthe art will be able to determine an appropriate “effective” amount inany individual case using routine experimentation and background generalknowledge. A therapeutic result in this context includes eradication orlessening of symptoms, reduced pain or discomfort, prolonged survival,improved mobility and other markers of clinical improvement. Atherapeutic result need not be a complete cure.

In the context of treatment and effective amounts as defined above, theterm subject (which is to be read to include “individual”, “animal”,“patient” or “mammal” where context permits) defines any subject,particularly a mammalian subject, for whom treatment is indicated.Mammalian subjects include, but are not limited to, humans, domesticanimals, farm animals, zoo animals, sport animals, pet animals such asdogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, goats,cows; primates such as apes, monkeys, orangutans, and chimpanzees;canids such as dogs and wolves; felids such as cats, lions, and tigers;equids such as horses, donkeys, and zebras; food animals such as cows,pigs, and sheep; ungulates such as deer and giraffes; and rodents suchas mice, rats, hamsters and guinea pigs. In preferred embodiments, thesubject is a human.

As used herein, the term “denuding” should be understood to meanmechanical removal or irreversible functional destruction of thesuperficial layer of an inner luminal surface of a body lumen along asection of the body lumen. When the body lumen is a vessel or vein, thesuperficial layer of the inner lumen is generally a single layer ofsquamous cells known as the vascular endothelium and its associatedconnective tissue extending to the superficial cell layers of the mediabut not deeper than the media layer. The endothelium is required for thesurvival of the body lumen as it provides a selective barrier andanti-thrombotic surface, the removal of which results in the exposure ofpro-thrombotic factors which interact with normal blood constituents tocause clotting and occlusion of the body lumen and release naturalvasoconstrictors into the lumen. When the body lumen is a vein, the termrefers to removal of one or more layers of the tunica intima layer andsuperficial media layer. The device and methods of the presentdisclosure denude a longitudinal section of a body lumen, for example1-60 cm, and denude the body lumen circumferentially; that is the fullcircumference (or partial or nearly the full circumference) if the bodylumen is denuded along a section being treated.

As used herein, the term “body lumen” means a cavity in the body, andmay be an elongated cavity such as a vessel (i.e. an artery, vein, lymphvessel, urethra, ureter, sinus, auditory canal, nasal cavity, bronchus,fallopian tube, spermatic duct) or an annular space in the heart such asthe left atrial appendage, left ventricular outflow tract, the aorticvalve, the mitral valve, mitral valve continuity, tricuspid valve,pulmonary valve, or heart valve, or venous valve, or valve opening.Preferably the body lumen is a vasculature (i.e. a vein or artery or anarterio-venous vessel). The vein may be selected from a saphenous vein(SSV, GSV, AASV), a pelvic vein, varicocele, or a portal vein. Theartery may be selected from an aorta, superior rectal artery, a sectionof artery intended for stenting for full or partial embolisation, auterine artery, or a ductus arteriosus. The body lumen may be a sectionof the gastrointestinal tract, for example the duodenum, smallintestine. The body lumen may be the oesophagus.

As used herein, the term “elongated catheter member” should beunderstood to mean an elongated body having a distal end that isoperably connected to the body lumen denuding body. In one embodiment,the catheter member comprises a control arm (for example a tubularmember) operably connected to the denuding body for control thereof. Thecontrol arm may take any form, for example, a rod, wire, or tubularmember such as a hypotube. In one embodiment, the control arm anddenuding body are axially adjustable relative to the catheter member.The denuding body is generally uncoiled and stowed in a distal end ofthe catheter member during delivery and withdrawal. Axial adjustment ofthe control arm relative to the catheter body results in deployment ofthe denuding body in its coiled configuration.

“Transluminal delivery” means delivery of the body lumen denuding bodyto a target site (for example a varicose vein) through a body lumen, forexample delivery through an artery, vein, or the gastrointestinal tract.

As used herein, the term “coil” should be understood to mean aloop-shaped element that is adjustable from an uncoiled configurationsuitable for retraction into a catheter member and coiled configurationthat in use is capable of circumferentially engaging and impressing itssurface against a body lumen (i.e. engage the internal lumen of the veinalong at least one full turn of the coil). The coil in its coiledconfiguration is generally circular, but may also be oval, square,triangular, or rectangular, as long as it is capable ofcircumferentially engaging an inner wall of the body lumen. As mostveins and arteries have a circular, or almost circular, profile, acircular coil is preferred, as the radial force exerted by the coil inits deployed configuration is spread evenly around the wall of the bodylumen. A coil having a diameter equal or greater than the diameter ofthe body lumen to be treated along at least one full turn of the coil isrequired to achieve circumferential engagement with the internal lumenof a vein, and thereby achieve circumferential denuding of the vein (seeA in FIG. 13). In a preferred embodiment, the coil is a helical coilhaving at least one full circumferential turn, and preferably from 1 to3 turns, for example about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9,2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, or 2.9 turns. The coils ofthe helical coil are preferably circular, but may also have anotherprofile, for example oval, square, triangular, or rectangular. Thehelical coil may be conical. The diameter of the coil is typically 2-20mm, more preferably 3-12 mm, in a relaxed state. The pitch of thehelical coil is typically approximately the same as the diameter, but itmay vary from 0.5 to 1.5 times the diameter, in a relaxed state. It willbe appreciated that the dimensions of the coil may be varied dependingon the body lumen, to ensure that the coil is “oversized” with respectto the diameter of the body lumen. In this regard, the diameter of thecoil (or the maximum diameter in the case of helical coils whosediameter varies along its length) is generally at least about 5% greaterthan the diameter of the body lumen to be treated, for example at least10%, 15%, 20%, 25% or 30% the diameter of the body lumen to be treated,and typically from 5-30% greater. It is important that the coil isoversized along at least one turn of the coil, and typically oversizedalong 1-2 turns. The coil may be formed from an elongated element,typically a single elongated element, for example a wire or filament.The coil may be formed from a metal (for example stainless steel) ormetal alloy, or it may be formed from a shape-memory alloy such asNITINOL, or it may be formed from a natural, synthetic or semi-syntheticpolymer such as chitosan, nylon or rayon. The body lumen denuding headideally consists of a single coil element, although in certainembodiments the coil may comprise a plurality of coil elements, forexample 2, 3, 4, 5, 6, 7, 8, 9 or 10, and preferably 2-4 coil elements.

The width of the coil element is at least 0.1mm. The width is typically1 to 3 mm to allow delivery via an appropriately sized catheter andintroducer sheath.

Typically, the helical coil is sufficiently resiliently deformable tomaintain a circumferential radial force against the wall of the bodylumen of varying diameter as it travels along the body lumen (i.e. it isconfigured to “self-adjust” or is “self-adjustable”). This isillustrated in FIGS. 59A-59C which illustrate the use of a device of thepresent disclosure to denude a vein with several bends and a diameterthat progressively increases. In this embodiment, the helical coil inits deployed state will be oversized with respect to the widest part ofthe body lumen, thereby exerting a radial force around the fullcircumference of the body lumen at its widest point shown in FIG. 59C,and is sufficiently resiliently deformable for the coil diameter toadjust to varying diameter of the vein while maintaining a denudingradial force against the circumference of the body lumen. The helicalcoil is typically sufficiently resiliently deformable to allow the coilpass through constrictions or valves in veins, as illustrated in FIGS.56A-C and 57A-C, respectively. These constrictions or changes in veindiameter over the treatment length may be either static (wider diameterof proximal vessel tapering to narrower distal vessel) or dynamic(contraction of vein wall smooth muscle leading to reduced vein diameterin a physiological process known as venospasm). The reducing veindiameter will increase the radial forces on the helical coil, this willin turn increase the hoop force generated within the material of thehelical coil which will translate as a longitudinal force to increasethe length of the coil. This concept is illustrated in FIGS. 60A-C wherethe device is shown deployed in a typical vessel over a length I anddiameter D. The radial force is equivalent to the pressure P actingperpendicular to the vein wall. The pressure that the vessel exerts onthe oversized coil or hoop force (HF) is acting to compress the coil andincreases when the diameter of the vessel is reduced to d. Due to theopen helical coil design this increased hoop force will translatelongitudinally to lengthen the coil to a length L. This will allow areduction of the radial forces at the contact point of the device outersurface with the vein wall to prevent excessive friction but maintainsufficient force to keep the surface engaged and impressed against thevein. Excessive friction can lead to undesirable catching or snagging ofcoil segments and wall perforation and/or trauma to connective tissueadjacent to the vein.

As used herein, the term “coil element” refers to individual andseparate coil elements that together make up the coil part of a deviceof the present disclosure. Typically, each coil element is helical.Typically, the coil elements are co-axial. Typically, each coil elementhas the same diameter when deployed. Typically, each coil element hasthe same pitch when deployed. When in a deployed configuration, theplurality of coil elements together provide circumferential engagementof the inner lumen of the body lumen. Thus, each coil element may beconfigured such that, in a deployed configuration, it engages only apart of the circumference of the inner lumen, for example 90°-270°,90°-180°, 140°-220°, or 180°-270°, of engagement with the circumferenceof the body lumen. In one embodiment, the coil has two helical coilelements, for example a double helix. Typically, each of the two helicalcoil elements has at least 0.5 turns when deployed, and typically from0.5 to 1.0 turns or 0.5 to 0.7 turns. In one embodiment, the coil hasthree helical coil elements, for example a triple helix. Typically, eachof the three helical coil elements has at least 0.3 turns when deployed,and typically from 0.3 to 1.0 turns or about 0.3 to 0.5 turns, whendeployed. In one embodiment, the coil has four helical coil elements.Typically, each of the four helical coil elements has at least 0.25turns when deployed, and typically from 0.25 to 0.75 turns whendeployed. In one embodiment, the plurality of coil elements areconnected together at their distal ends (closed configuration). In oneembodiment, the plurality of coil elements are unconnected at theirdistal ends (open configuration).

As used herein, the term “non-detachably attached to the cathetermember” as applied to the body lumen (or vessel or vein) denuding headshould be understood to mean that the device is not configured todetachment and release of the head from the catheter member in the body;in other words, the device is not configured to implantation of the bodylumen denuding head in the body.

Implantable devices are undesirable for use in the treatment ofsuperficial venous disease for the following reasons; Superficial legveins are located relatively close to the skin surface where they can beeasily palpated to touch. Bulky implantable devices can potentiallycause pain, irritation or local skin deformity; Implants may inhibit theability of the vein to reduce its diameter by contraction of smoothmuscle known as venospasm. This is important in reducing vein diameter,reducing the amount of thrombus within the vein and preventingrecanalisation; Implants may cause immune mediated inflammatoryreactions.

The body lumen engaging surface of at least part of the coil is abrasivefor shearing or irreversibly damaging an inner lining of the body lumenaway from the body lumen. The surface may be treated chemically,electrically or physically/mechanically to make it abrasive. There areseveral types of machining that can be adopted in order to roughen thesurface including mechanical abrasion, shot blasting, sand blasting,knurling, electrical discharge machining, and pulse electrochemicalmachining. Chemical etching can also be used to roughen the surface ofthe part. The surface may be serrated. The surface could also includeraised portions that when contacting the vessel lumen act as an abrasivesurface, these raised portions could be pieces bonded to the surface ofthe abrasive surface or sections that are folded up from the abrasivesurface, or pitted indentations that have a grating effect. One way ofproviding a helical coil having an abrasive surface is to wrap a secondwire, or multiple wires, helically around a core wire as described belowand shown in the figures. The second wire may have a round, flat,polygonal, triangular, square, rectangular, x-shaped, or star-shapedcross-section, so long as the combination of the elongated element (corewire) and the helically wound second wire create an abrasive lumenengaging surface capable of denuding the lumen when moved axially alongthe lumen in the deployed configuration. Wires may not be the only typeof material wrapped around a central core wire or central housing, forexample a polymer-based moulding, fins, abrasive granules, or spotwelds. Another way of making a serrated surface is to score indentationsin the surface of the coil, or to fabricate raised formations on thesurface, for example helical indentations or formations. The surfaceshould be abrasive enough so as to denude the lumen following a singlelongitudinal passage of the device to avoid the requirement of multiplepasses which could be restricted by initial vasospasm. A preferredconfiguration includes surface elements to create both a macro and microabrasive surface. The macro abrasive surface comprises grooves,indentations or teeth of at least about 0.5 mm in height (for example.0.5 to 1.0 mm) from peak to trough. The micro surface comprises grooves,indentations or teeth of about 5 to 100 microns in height from peak totrough. These grooves cause abrasion and prevent clogging of theabrasive surface by cellular debris over the treatment length. Theorientation of the macro abrasive grooves is important as they shouldnot be parallel but perpendicular to the axial direction of withdrawal.This is illustrated in FIG. 64 which shows a device deployed in avessel. A detailed view of the coil surface is shown in the enlargedviews in FIGS. 64B, 64C, and 64D. FIG. 64B illustrates a groove patternperpendicular to the vessel wall on withdrawal which is effective forcausing mechanical ablation. FIG. 64C shows an orientation that liesparallel to the vein wall during withdrawal and is less effective. Dueto the variability in vessel diameter and tortuosity in venous anatomy amacro-abrasive texture pattern in required to overcome this problem.FIG. 64D illustrates a diamond knurled pattern which is ideal to ensurepart of the macro abrasive surface is always perpendicular to the veinwall during engagement when the device is withdrawn axially. The microabrasive surface may have a surface roughness or RA value typicallybetween 0.8 and 3.2 to achieve endothelial disruption and preventexcessive static friction. The RA value is the arithmetic average of theabsolute values of the profile height deviations from the mean line,recorded within the evaluation length. An RA value of 0.8 corresponds toaverage peak to trough heights of 4 μm. Endothelial Cells (ECs) areprotected in most vessels from direct exposure to flowing blood by anacellular layer known as the glycocalyx. This gel like structure istypically of thickness 0.5-3 μm, exceeding that of the ECs (0.2-2.0 μm)themselves.

As used herein, the term “shape memory material” should be understood tomean a material, typically a metal alloy, that remembers its originalshape and that when deformed or forced into a different configuration,returns to its pre-deformed shape when deformation forces are released.An example is Nitinol. In one embodiment, the coil, or the core elementof the coil, is formed from a shape memory material. Methods for makingthe coil from a shape memory material generally involve the stepswrapping the shape memory alloy around a die or heat setting fixture soit forms the desired shape post heat setting, placing the loaded fixtureinto an oven for a set temperature/time and the removing and cooling thepiece. It is also possible to form the shape from a cylindrical piece oftubing that is laser cut to the desired size. It may also possible tofabricate this shape memory by other means, for example electroactivated polymers.

As used herein, the term “treatment zone” as applied to a body lumen,vessel or superficial vein refers to a cylindrical section of a bodylumen that is involved in the pathogenesis of a disease state and istypically 1cm or greater in length. In the context of a superficialvein, the term “treatment zone” should be understood to mean acylindrical section of the lumen of the superficial vein that fails tocirculate blood effectively, and is typically 1 cm or greater in length.In one embodiment, the treatment zone is 1-50 cm, 1-40 cm, 1-30 cm, 1-25cm, 1-15 cm, 1-10 cm, 5-50 cm, 5-40 cm, 5-30 cm, 5-25 cm, 5-15 cm, 5-10cm, 10-50 cm, 10-40 cm, 10-30 cm, 10-25 cm, or 10-15 cm, in length.

As indicated in FIG. 1, veins comprise of 3 primary cellular layers: anouter adventitia layer made up of tough fibrous tissue and unmyelinatednerve fibres, a media layer made up of collagen and smooth muscle cellsand an inner endothelial layer comprised of a single layer of squamouscells and some connective tissue. In addition, the endothelial layer iscovered by the acellular glycocalyx which is typically an evenlydistributed structure of thickness 0.5-3 μm.

Veins have thinner walls than arteries and are less rigid and morecompliant. Unlike arteries which retain their cylindrical shape at alltimes, veins can empty of blood and collapse down or alternativelystretch significantly to accommodate increased volumes of blood.

Vein spasm or constriction occurs in response to physical stretchactivating nerves on the outside of the vein wall. Constriction alsooccurs when chemicals such as endothelin-1 are released by theendothelium in response to stretch or disruption.

The endothelial layer prevents blood from clotting in veins. If theendothelium is disrupted or damaged, pro-thrombotic factors are exposedwhich platelets will immediately adhere to and the clotting cascade willbegin. Over time (4-12 weeks, typically an average of 8 weeks) clotwithin a vein becomes fibrotic as it is invaded by surrounding cellswhich deposit fibrin and collagen in a process known as sclerosis orfibrotic transformation. This prevents blood reflux in the vein and thussuccessfully treats the varicose vein.

The aim of the device is to disrupt the endothelial and media layers ofthe vein but not the outer adventitia layer. This requires selectivecontrolled mechanical disruption to a depth of at least 5 μm and up tobut not exceeding 100 μm. This ensures endothelial and superficialmedial layer disruption without deeper media/adventitial disruptionwhich can lead to pain and/or perforation. There may be further celldeath in deeper layers due to intracellular content release causingapoptosis in adjacent cells and continuing in a cascade over time to adepth of up to 300 μm. The resultant thrombosis or clot and fibrous scartissue prevents blood from entering the vein and thus the appearance andsymptoms associated with varicose veins. It is important that theendothelium is completely circumferentially disrupted as if small areasare left intact, clot may not form and blood will continue to flowleading to treatment failure and/or early recurrence. This is likely tooccur when liquid or foam chemical sclerosants are used in large veinsand is the suspected cause of poor efficacy rates of only 70% comparedto 90-98% with thermal treatments.

As the treatment begins two or more centimetres back from the junctionto the deep veins, the attached created thrombus is confined to thesuperficial vein and as there is no blood flow it cannot be carried intothe deep system where it can cause complications.

The precise requirements for successful long-term vein ablation arecurrently unknown. Some experts in the treatment of superficial venousreflux propose that complete endothelial damage is sufficient. Thisleads to thrombus formation and discontinuation of blood flow, the bodythen converts the thrombosed vein into a fibrous cord in a process knownas sclerosis or fibrotic transformation, achieving long-term ablation.Others argue that damage of vein wall tissue into the deeper medialayer, in addition to the inner intima layer, is required for long-termvein ablation. Others such as thermal ablation proponents propose thatcomplete transmural damage of the vein wall from the intima to the outeradventitia layer is required.

A device of the present disclosure may achieve complete circumferentialendothelial damage by its oversized coiled configuration with abrasivesurface. It also causes media layer damage by at least three separatemechanisms. Firstly, the abrasive polygonal coil surface can penetrateto over 50 μm allowing damage to occur deeper than the intima layer.This could also be further increased by the use of more than one coilallowing the second abrasive coil, located more distally on the device,to penetrate deeper into the vessel wall section that has already beendenuded by a coil more proximally on the device. This could also beachieved by repeating the procedure over the same treatment length usingthe same device. Secondly, it has been shown in studies of foamsclerotherapy that cell death occurs up to 300 μm into the vein wall[10]. This is likely due to a cascading effect of cell death caused byrelease of molecules by damaged cells signalling apoptosis to occur inneighbouring cells. In this manner cell vein wall damage can occurdeeper to the superficial cells affected by mechanical destruction.Thirdly, frictional forces caused by the device acting on superficiallayers combined with resistance of deeper media layers have a shearingeffect within the vein wall layers resulting in deeper vessel walldamage. This effect has been reported in previous studies and was alsoseen on pre-clinical testing of the present disclosure.

The risk of vein rupture and/or snagging of the device is proportionalto the abrasiveness or sharpness of the device in contact with the wallcausing frictional or cutting forces respectively and the depth that theabrasive elements penetrate into the wall. Snagging is a commonlyreported pain point for physicians and patients following the use ofcurrent mechanochemical devices. There are even documented cases wherethe vein was snagged and stripped out inadvertently leading to pain andhaematoma formation known as “inadvertent spontaneous stripping” [6].Vein valve leaflets also represent an obstacle where a mechanical tipcan become stuck and lead to snagging.

The key problem therein is the difficulty in completely removing theendothelial layer and partially damaging the media layer without causingexcessive resistance and/or snagging.

FIG. 2 highlights the importance of circumferential coverage in terms ofendothelial cell destruction. It is taken from a partially treated veinin our animal study. The upper right corner shows a clot adherent to thevein wall with tissue invasion as it starts to become fibrotic at 28days post procedure. The lower left corner has intact endotheliumremaining. No clot has formed and blood can flow in the channel leadingto overall treatment failure in this segment. Conversely, FIG. 3illustrates the results of full endothelial coverage and damage at 28days post procedure with adherent thrombus formation obliterating theentire vessel lumen preventing blood flow resulting in treatmentsuccess. Inflammatory cell migration from the adventitia into thethrombus can be identified on microscopic examination. This leads tofibrotic transformation of the thrombus and long-term occlusion.

Devices and methods of the present disclosure will now be described withreference to specific embodiments. These are merely exemplary and forillustrative purposes only: they are not intended to be limiting in anyway to the scope of the claimed invention. These examples constitute thebest mode currently contemplated for practicing the invention.

Referring to the drawings, and initially to FIGS. 4 to 7, there isillustrated a device according to the present disclosure for denuding abody lumen, indicated generally by the reference numeral 1. The device1, which in this embodiment, is a device for denuding a varicose veinfor the purpose of causing occlusion of the vein and thereby treatingthe varicose vein, comprises a polyimide catheter member 2 and adenuding head 3 configured for transluminal delivery to a section of avaricose vein to be treated, and deployment at the target location inthe vein. The denuding head 3 comprises a helical coil 4 having aproximal end 5 and a distal end 6, which are generally co-axial with anaxis of the helical coil, and a coiled part having about 1.5 rotations,an outer diameter of 13 mm, and a pitch of about 9 mm.

The helical coil 4 is axially adjustable with respect to the cathetermember from a delivery configuration (not shown) in which the coil isunwound and stowed in a distal end of the catheter member 2, and adeployed, coiled, configuration, shown in FIGS. 4 to 7. The helical coilcomprises a shape memory alloy, and is biased to assume the coiledconfiguration when it is extended beyond the distal end of the cathetermember. The device is suitable for use in a varicose vein having anormal diameter of 4-12 mm (i.e. where the coil is oversized with regardto the vein to be treated).

It will be noted that the “oversized” diameter of the helical coilextends along at least one full loop of the coil (360 degrees). Thisfeature, added to the oversized diameter of the coil relative to thevein, ensures that the coil engages and impresses circumferentiallyagainst the inner lumen of the vein, exerting radial pressure evenlyaround the full circumference of the vein. It is possible for theoversized diameter to extend along less than one full loop, for exampleat least 300 degrees, however this leads to a risk that the inner lumenof the vein will be incompletely denuded resulting in partial veinocclusion and subsequent recanalisation. In this embodiment, the coilhas just over one complete turn, to allow complete coverage even whenstretched while not being too long to cause increased friction againstthe vein wall and snagging. The addition of further coil turns in alonger coil can be used to induce further mechanical damage into thevein wall. The increased surface area of the device in contact with thevein in such an embodiment would also increase the risk of snagging andvein wall damage. Therefore, a coil with just over one complete turnrepresents the most efficient method of attaining complete denudation ofthe vessel inner surface.

The coiled configuration and flexible material of the denuding headallows it to adapt to different vein diameters within a range of sizeswhich are smaller than the diameter of the coil while still exertingadequate radial force to cause denudation. These properties also enablethe coil to adapt to changing vein diameters within the same vein overits target treatment length. These changes may be due to the naturaltapering of the vein or due to venous valves. The latter can causesignificant snagging and vein perforation if rigid structures becomecaught or trapped by the valve leaflets. Due to the flexible nature ofthe coil and minimal protrusions of the abrasive components this isunlikely to occur. In the event of the device being caught by valveleaflets, a resultant small increase in force along the longitudinalaxis will automatically decrease the diameter of the coil, whileincreasing its length, allowing the coil to free itself and avoidsnagging or detaching the valve and associated leaflets, illustrated inFIGS. 60A-60C and 61A-61C. This will occur automatically during normalwithdrawal of the device within the vein and does not requireadjustment, extra manoeuvres or supplementary imaging to be performed bythe operator.

Referring to the drawings, and initially to FIGS. 8 and 9, the helicalcoil 4 has an abrasive surface configured to shear the inner lining ofthe vein (primarily but not limited to the endothelial cell layer) awayfrom the vein when the helical coil is moved axially along the vein whenin a deployed configuration. In this embodiment, the helical coilcomprises a 0.01181″ NITINOL core wire 8 and a second wire 9 helicallywound around the core wire 8 forming an abrasive, serrated, surface onthe helical coil 4. Referring to FIGS. 8 and 9, the second wire 9 is aflat wire that is formed from stainless Steel or Nitinol. In thisembodiment, the core wire 8 has a diameter of about 1 mm and the secondwire 9 has width of about 0.7 mm and a thickness of about 0.02 mm. Thepitch of the second wire is about 1.5 mm. Referring to FIG. 9, the pitchof the second wire 9 on the core wire 8 reduces at the distal end 6 ofthe helical coil 4, in this case to about 0.3 mm. The purpose of thesmaller pitch/closed pitch at the distal end is to form a flexibledistal member of the device to help navigate the device to the targetanatomy. Referring to FIG. 10, the pitch of the second wire 9 on thecore wire 8 increases at the proximal end 5 of the helical coil 4, inthis case to a maximum of about 3 mm. The purpose the higher pitch atthe proximal end is to assist in the smooth recapture of the distal tipfollowing the procedure. This proximal partition could also have aclosed section with a lower, tighter pitch to aid recapture.

The thickness of the second wire 9 is between 0.1 and 1 mm. Based ontesting using equivalent animal venous tissue, a diameter of greaterthan 1 mm will carry the risk of creating a surface protrusion which cansnag or stick to the vein wall surface.

Referring to FIGS. 10 and 11, the proximal end 5 of the coil 4 isattached to a stainless steel hypotube 12 which extends through thecatheter member 2 to a proximal end thereof (not shown). In use, thehypotube 12 can be axially adjusted with respect to the catheter member2 to effect deployment of the helical coil 4 distally of the cathetermember into the coiled configuration, and retraction of the helical coil4 into the catheter member during transluminal delivery and withdrawalof the device. In this embodiment, the catheter member 2 is 4 Frpolyimide extruded catheter tube, having an inwardly tapering mouth 14in FIG. 11 to assist in recapturing the helical coil 4 when it isretracted into the catheter member 2.

Referring to FIG. 9, the distal end of the helical coil 4 terminates inan atraumatic head, in this embodiment provided by a smooth metal ball15, which serves to prevent the helical coil snagging on a vein or valveand reduce the risk of the distal tip causing perforation to the veinwall when it is deployed and withdrawn. In addition, referring to FIG. 9the ball 15 is dimensioned to nest in the tapered mouth 14 in FIG. 11 ofthe catheter member 2 when the device is in the delivery configuration.

Referring to FIG. 9, between the end of the abrasive coil and the distalsmooth ball there is an elongated straight section of approximately 5 mmto aid navigation and placement of the device. The ball at the distalside of the device forms an atraumatic tip, in another embodiment thiscan be the same diameter as the diameter of the abrasive member so as tonot create a ball but a straight atraumatic tip.

Referring to FIG. 12 there is illustrated part of a device according toan alternative embodiment of the present disclosure, in which partsidentified with reference to the previous embodiments are assigned thesame reference numerals. In this embodiment, a surface of the secondwire is scored with helical indentations 20 which serve to provide anabrasive, serrated, surface on the helical coil 4.

Referring to FIGS. 13 to 19, the use of the device of the presentdisclosure is illustrated. In the following description proximal refersto toward the access insertion site while distal refers to away from theaccess site in the blood vessel. The device can be delivered and removedthrough a single injection site and does not require any implantation oradministration of chemical agents. The method of treating a vein withreflux to cause permanent occlusion may comprise the following steps.

In a first step, the device is adjusted into a delivery configuration,with the helical coil 4 retracted into the end of the catheter member(not shown). In some embodiments the catheter member is a polyimideextrusion. The device is then delivered to the target vein via aseparate introducer catheter under image guidance, for exampleultrasound.

The device is then navigated distally under ultrasound guidance to therequired position. The correct placement, with a distal end of thecatheter member 2 positioned at the beginning of the vein to be treatedis verified by ultrasound shown in FIG. 17.

The outer catheter 2 is axially withdrawn exposing the helical coil 4and hypotube 12, to a deployed coiled configuration shown in FIG. 13. Insome embodiments, the helical coil is deployed using a handle with athumbwheel-controlled element. Using a single handed, intuitive movementthe operator can deploy the coil by turning the thumbwheel with thethumb of the hand which holds the handle. This allows simultaneousvisualisation by positioning of an ultrasound probe using the oppositehand. This enables the physician to perform the procedure without anassistant if required.

The coil in both its undeployed and deployed configuration must beeasily visualised on ultrasound to prevent inadvertent placement. Thisis achieved by incorporation of an echogenic section of material ontothe tip of the catheter. In the deployed state the coil with itsabrasive surface is inherently echogenic.

As the coil is oversized with respect to the vein being treated, itexerts an outward radial force against the lumen of the vein along atleast one full circumference of the vein.

Unlike current treatment options, the action of the device on the veinwall to cause long term occlusion only occurs following withdrawal ofthe device in the vein section to be treated. This can only occur in theproximal direction which protects the more distal structure which mayinclude veins in the deep system.

If the device is inadvertently placed in the wrong position of thetarget vessel it can be recaptured into the outer catheter andrepositioned without causing vessel trauma.

The device is then moved proximally along the section of the vein to betreated (generally a segment of vein of about 10 to 70 cm), where theradial force of the abrasive surface of coil against the inner lumen ofthe vein, and the axial movement, causes the helical coil to remove,destroy or disrupt the superficial layers of the inside of the innerlumen of the vein. These layers consist of the glycocalyx, endothelium,sub endothelial connective tissue and superficial layers of the medialayer. Stretch receptors in the vein wall respond to the devices outwardradial force leading to vasospasm. This is further enhanced by releaseof chemical agents stored within endothelial cell bodies, mainlyendothelin-1, a powerful vasoconstrictor. Exposure of subendothelialcollagen leads to platelet adhesion and triggers a cascade activation ofprothrombotic factors leading to thrombotic occlusion of the vessel.This thrombotic occlusion is further enhanced by significant vasospasmas shown in FIG. 19 where the treated vein section is significantlycontracted in the acute stage. This results in a complete termination ofblood flow in the vessel. This was demonstrated during a pre-clinicalstudy on a goat lateral saphenous vein in which high pressure manualinjection of contrast material did not enter the vein 45 minutes posttreatment.

Not to be limited by theory, circumferential endothelial layerdestruction allows intraluminal thrombosis to adhere directly to thevessel wall and causes recruitment of cells involved in the inflammatoryhealing response to migrate from the adventitia across the lumen andinto the thrombus. These cells include fibroblasts which create collagenin the thrombotic occlusion converting the vessel into a fibrotic cordover time. This leads to long-term closure of the vessel and resolutionof venous disease symptoms.

Contrary to the previous belief that complete vein wall transmural celldamage is required, the inventors have demonstrated that superficialdenudation alone can cause a sufficient inflammatory reaction to inducefibroblasts on the outer adventitia layer to migrate inwards. This isadvantageous as it provides a mechanism of action that a device canutilise which doesn't cause the patient pain or require tumescent needlestick preparation injections to prevent pain. This is because thesensory pain nerve fibres are located on the adventitial layer of thevessel which is not directly affected by the device.

Results from the authors pre-clinical studies have also proven theimportance of full circumferential endothelial disruption in achievinglong term successful occlusion. Thrombotic occlusion without endothelialdisruption will lead to recanalisation even if the endothelium ispartially disrupted as shown in FIG. 2. This is because the endotheliumprevents thrombus adherence which causes thrombus shrinkage away fromthe vessel wall. This is further enhanced by nitric oxide secretion fromthe endothelial cells, promoting vasodilation thus counteracting theeffect of venospasm. This may be the primary factor involved in the lowefficacy rates of chemical sclerosant based techniques. As thesclerosant is deactivated by blood and removed by the velocity ofcirculation it can only cause incomplete endothelial disruptionespecially in larger vessels which have more blood and a greater surfacearea even in a collapsed state.

The embodiments of FIGS. 4 to 16 all have a body lumen denuding headformed from a single coil element that in a deployed configurationcomprises one full helical turn and in use circumferentially denudes aninner lumen of a body lumen. Referring to FIGS. 20 to 24, an alternativeembodiment of the device of the present disclosure is described,indicated generally by the reference numeral 30, and in which partsdescribed with reference to the previous embodiments are assigned thesame reference numerals. In this embodiment, the device includes anelongated control arm 31 that passes through the catheter member 2 andis operatively connected to a distal end 6 of the coil 4, and theproximal end 5 of the coil is attached to the stainless steel hypotube12. Axial movement of the control arm 31 relative to the hypotube 12effects deployment or uncoiling of the coil—FIGS. 22 shows the coil is apartly coiled configuration, and 23 shows the coil is a fully coiledconfiguration. The use of this embodiment is substantially the same asthat described previously, with the exception that the deployment of thecoil can be controlled by adjusting the axial position of the controlarm 31 and hypotube 12.

Referring to FIGS. 25 to 27, an alternative embodiment of the device ofthe present disclosure is described, indicated generally by thereference numeral 40, and in which parts described with reference to theprevious embodiments are assigned the same reference numerals. In thisembodiment, the coil 4 is composed of two coil elements 41 a and 41 bthat work in tandem to circumferentially denude an inner lumen of thebody lumen, each of which is adjustable from an uncoiled configurationsuitable for disposal within the catheter member and transluminaldelivery through a body lumen, and coiled configuration shown in theFigures. Each coil element 41 a, 41 b has a proximal part that isgenerally coaxial with the catheter member, and a coiled part that inits deployed configuration comprises less than one full turn such thecoil elements together adapt a double helix conformation that in usecircumferentially engages the body lumen to be treated. As with previousembodiments, each coil element comprises a core wire 8 having a secondwire 9 wrapped around the core wire to provide a serrated body lumendenuding surface. The use of this embodiment, is the same as thatdescribed with reference to the previous embodiments.

Referring to FIGS. 28 to 30, an alternative embodiment of the device ofthe present disclosure is described, indicated generally by thereference numeral 50, and in which parts described with reference to theprevious embodiments are assigned the same reference numerals. In thisembodiment, the coil 4 is composed of four coil elements 51 a-51 d thatwork in tandem to circumferentially denude an inner lumen of the bodylumen, each of which is adjustable from an uncoiled configurationsuitable for disposal within the catheter member and transluminaldelivery through a body lumen, and coiled configuration shown in theFigures. Each coil element 51 a to 51 d in its deployed configurationcomprises about one quarter of a full turn and the four coil elementstogether adapt a quadruple helix conformation, such that the four coilelements together circumferentially engage the body lumen to be treated.As with previous embodiments, each coil element comprises a core wire 8having a second wire 9 wrapped around the core wire to provide aserrated body lumen denuding surface. The use of this embodiment, is theas that described with reference to the previous embodiments.

In the embodiments described above that comprise more than one coilelement, the coil elements are joined at their proximal ends and havefree distal ends (i.e. open coils). It will be appreciated however thatthe coil may be a closed coil, where the coil elements are joinedtogether at the proximal and distal ends. Such an embodiment isdescribed in FIGS. 31-33, in which parts described with reference to theprevious embodiments are assigned the same reference numerals. In thisembodiment, the device 60 comprises a coil formed of four helical coilelements 61 a-61 d that are joined together at their proximal and distalends 5, 6, with each coil having about one half of a full turn. As withprevious embodiments, each coil element comprises a core wire 8 having asecond wire 9 wrapped around the core wire to provide a serrated bodylumen denuding surface. The use of this embodiment, is the as thatdescribed with reference to the previous embodiments.

FIGS. 34A to 41B illustrate helical coils forming part of devices of thepresent disclosure, and in particular different types of wires formingthe coils, and different types of indentations/formations on a surfaceof the coil forming the roughened surface. The coils are formed fromnitinol wire, and the indentations are cut using a knurling process.

Referring to FIGS. 34A and 34B, a section of a helical coil 67 isillustrated having a generally flat profile with an externallumen-engaging surface 61 with transverse indentations forming teeth 62having a truncated triangle profile, a flat internal surface 63, andsides cut in a zig-zag formation providing a multiplicity of lateralteeth 65.

Referring to FIGS. 35A and 35B, a section of a helical coil 70 isillustrated having a generally convex profile with an externallumen-engaging surface 71 with curved transverse indentations formingteeth 72 having a triangular profile, and a smooth convex internalsurface 73.

Referring to FIGS. 36A and 36B, a section of a helical coil 80 isillustrated having a generally flat profile with an externallumen-engaging surface 81 with transverse indentations formed on eachside 84 of the surface 81 providing two series of teeth 82 having atruncated triangle profile, and a smooth concave internal surface 83.

Referring to FIGS. 37A and 37B, a section of a helical coil 90 isillustrated having a generally convex profile with a convex externallumen-engaging surface 91 with indentations formed on the surface 91providing diamond-shaped teeth 92 some with flat tips and some withpointed tips, and a smooth flat internal surface 93.

Referring to FIGS. 38A and 38B, a section of a helical coil 100 isillustrated having a generally crescent-shaped profile with a convexexternal lumen-engaging surface 101 with curved indentations formed onthe surface 101 providing transverse teeth 102 having a scalenetriangular profile, and a smooth flat internal surface 103.

Referring to FIGS. 39A and 39B, a section of a helical coil 110 isillustrated having a generally oval-shaped profile with a convexexternal lumen-engaging surface 111 with curved V-profile indentationsformed on the surface 111 providing transverse teeth 102 having atriangular profile, and a smooth flat internal surface 113.

Referring to FIGS. 40A and 40B, a section of a helical coil 120 isillustrated having a generally flat profile with a flat externallumen-engaging surface 121, a flat internal surface 123, and sides cutin a zig-zag formation providing a multiplicity of lateral teeth 125.

Referring to FIGS. 41A and 41B, a section of a helical coil 130 isillustrated having a generally inverted T-shaped profile with a base131, teeth 132 disposed on the base, and a smooth flat internal surface133.

The above described surface patterns and shapes are advantageous as theyallow both the correct angle, depth, and level of cellular disruption tobe delivered during axial treatment of the body lumen wherein thedeployed device is automatically deformed in response to changes in thebody lumen diameter. As previously described the macro-abrasive surfaceshould ideally contact the vessel wall perpendicularly during withdrawalto have the greatest effect.

FIGS. 42A to 48C illustrate a number of vein denuding heads forming partof devices of the present disclosure, and in particular vein denudingheads having a single helical coil, and in which parts described withreference to previous embodiments are assigned the same referencenumerals.

FIGS. 42A and 42B illustrate a vein denuding head forming part of adevice of the present disclosure, and indicated generally by thereference numeral 140, and comprising a control arm 31 and helical coil141 having approximately three turns and a proximal section 142 wherethe coil increases in diameter towards a mid-point 143 and a distalsection 144 where the diameter of the coil decreases in diameter towardsa distal tip 145 which is disposed on an axis of the helical coil.

FIGS. 43A and 43B illustrate a vein denuding head forming part of adevice of the present disclosure, and indicated generally by thereference numeral 150, and comprising a control arm 31 and helical coil151 having approximately three turns (coils) 152A, 152B, 152C each ofwhich has a slightly different diameter and is slightly offset, axially,relative to the preceding turn.

FIGS. 44A and 44B illustrate a vein denuding head forming part of adevice of the present disclosure, and indicated generally by thereference numeral 160, and comprising a control arm 31 and helical coil161 having approximately seven turns (coils) with varying diameter andincluding a proximal section 162 where the coil initially decreases andthen increases in diameter towards a mid-point 163 and a distal section164 where the diameter of the coil decreases in diameter towards adistal tip 165.

FIGS. 45A and 45B illustrate a vein denuding head forming part of adevice of the present disclosure, and indicated generally by thereference numeral 170, and comprising a control arm 31 and helical coil171 having approximately four turns (coils) and comprising a proximalcoil element 172, distal coil element 173, and transition member 174connecting the coil elements, and a distal tip 175.

FIGS. 46A and 46B illustrate a vein denuding head forming part of adevice of the present disclosure, and indicated generally by thereference numeral 180, and comprising a helical coil 181 havingapproximately two turns (coils) and comprising a proximal coil element182, distal coil element 183, and transition member 184 including astraight section connecting the coil elements, and a distal tip 185.

FIGS. 47A and 47B illustrate a vein denuding head forming part of adevice of the present disclosure, and indicated generally by thereference numeral 190, and comprising a control arm 31 and helical coil191 having approximately three turns (coils) that decrease in diameterdistally towards the distal tip 195.

FIGS. 48A, 48B and 48C illustrate a vein denuding head forming part of adevice of the present disclosure, and indicated generally by thereference numeral 200, and comprising a control arm 31 and helical coil201 having approximately three turns (coils) and comprising a proximalright-handed coil element 202 of about two turns, a distal left-handedcoil element 203 with about 1.5 turns, and transition member 204 with aturn section 206, and a distal tip 205. The turn section 206 allows thesmaller diameter right-handed proximal coil 202 transition to a largerdiameter left-handed distal coil 203.

FIGS. 49A to 51A illustrate a number of vein denuding heads forming partof devices of the present disclosure, and in particular vein denudingheads have two unconnected helical coils axially spaced apart, in whichparts described with reference to previous embodiments are assigned thesame reference numerals.

FIGS. 49A and 49B illustrate a vein denuding head forming part of adevice according to the present disclosure, indicated generally by thereference numeral 210, and comprising a control arm 31 which isbifurcated at a distal end to provide control elements 31A and 31B, aproximal helical coil 211 operatively attached to control element 31Aand a distal helical coil 212, axially spaced apart from the proximalhelical coil, and operatively attached to control element 31B thatpasses through the proximal helical coil. Each helical coil has slightlymore than two turns (coils) and is generally conical with a diameterthat increases proximally.

FIGS. 50A and 50B illustrate a vein denuding head forming part of adevice according to the present disclosure, indicated generally by thereference numeral 220, and comprising a control arm 31 which isbifurcated at a distal end to provide control elements 31A and 31B, aproximal helical coil 221 operatively attached to control element 31Aand a distal helical coil 222, axially spaced apart from the proximalhelical coil, and operatively attached to control element 31B thatpasses through the proximal helical coil. Each helical coil has slightlymore than two turns (coils) and is generally conical with a diameterthat increases proximally. In addition, the maximal diameter of theproximal coil d1 is approximately three times the maximal diameter ofthe distal coil d2, and the pitch of the distal helical coil p1 is abouttwo times that of the proximal helical coil p2.

FIG. 51A illustrates a vein denuding head forming part of a deviceaccording to the present disclosure, indicated generally by thereference numeral 230, and comprising a control arm 31 which isbifurcated at a distal end to provide control elements 31A and 31B, aproximal helical coil 231 operatively attached to control element 31Aand a distal helical coil 232, axially spaced apart from the proximalhelical coil, and operatively attached to control element 31B thatpasses through part of the proximal helical coil. Each helical coil hasslightly more than two turns (coils) and is generally conical with adiameter that increases proximally. In addition, the maximal diameter ofthe proximal coil is approximately one third of the maximal diameter ofthe distal coil, and the pitch of the distal helical coil is about halfthat of the proximal helical coil.

Referring to FIG. 61A when the coil is deployed and engages the internalsurface of the vessel lumen there is static friction between the deviceand the vessel wall. At rest there is an outward radial force at thecoil contact points (FC) which is proportional to the stiffness anddiameter of the coil and the diameter of the vessel. This iscounterbalanced by a constraint force of the vessel P. As the userwithdraws the device the axial force, FA, increases to overcome staticfriction. In sliding systems between solid objects the friction force isproportional to the loading contact force (FC) and surface roughness,described by Amontons' law of friction. It has also been shown thatcontact surface area is a factor which increases friction [11].

Ideally as the axial force (FA) increases, static friction is overcomebefore the coil begins to lengthen. Static friction in veins andarteries is generally low due to the presence of the gel like glycocalyxlayer which has been shown to reduce static friction [12]. When thevessel constraint force is increased as in venospasm, a greater axialforce is required which leads to lengthening of the coil while stillremaining in contact with the vessel wall due to its resilientdeformability as illustrated in FIG. 61B. The axial force required tocause coil lengthening is proportional to the wire stiffness and is alsoaffected by the wire profile (flat vs round).

In some instances, as illustrated in FIG. 61C, there is significantconstraint force on the device due to excessive venospasm or naturalobstructions due to vein valves. The increased constraint force isusually focused on a distal portion of the coil in this situation. Asthe axial force increases further the coil reduces its diameter enoughto lose contact with the vessel wall as illustrated in FIG. 61C. Thisdramatically reduces static friction and can narrow the distal end toallow it to overcome static friction and/or an obstruction. When thisoccurs the coil jumps or skips proximally during recoiling to adopt itsnatural configuration. This can cause small sections of vein wall to bemissed by the abrasive surface. In some instances, such as passingthrough very narrow constrictions or vein valves, some coil deformationcausing loss of contact is desirable to allow the coil to reduce staticfriction before the axial force becomes too high as to cause vessel walldamage or vein stripping. Vein stripping occurs when the distal tip ofan intraluminal device acts like an anchor to transmit axial forceswhich are great enough to strip or remove an entire vein segment fromthe surrounding tissue. This has been documented with previous devicesfor vein ablation that have a non-deformable less elastic designs andcauses significant pain and bruising for the patient as well ascomplicating the procedure [6].

To overcome excessive coil lengthening and resultant skipping, variablesrelated to static friction and coil deformability can be modified byaltering the thickness, shape, diameter and/or stiffness of the deviceelement. The surface roughness should remain constant to achievesufficient mechanical ablation.

The use of other coil configurations can also limit the effect ofskipping on endothelial coverage. Such embodiments of the device areillustrated in FIGS. 42A to 51A. FIGS. 45A-45B and 46A-46B incorporate acoupling segment (174,184) which can act to prevent excessivelengthening across the entire coil. FIGS. 48A-48C illustrate a couplingsegment between coils with opposing clockwise and anti-clockwiseconfigurations to resist excessive lengthening. FIGS. 49A to 51Aillustrate separate coil elements to provide coverage should either coilelement be exposed to excessive static friction and lose contact duringlengthening.

Referring to FIG. 63, in another embodiment there is a single flat wireoption. This flat wire is formed from Nitinol. The outer surface of thiswire is textured (roughened) using a knurling process that presses ashape into the wire, similarly the texture can be applied by other meansfor example stamping or micro machining. This creates abrasive featuresin the wire. Reference FIG. 37A which shows a diamond knurl patternpressed into the Nitinol wire. The wire outer surface can also be shotblasted to create a micro-abrasive surface on the wire. This flat wireis subsequently held in a heat setting fixture and shape set in ahelical profile. The helical coil with its abrasive outer surface isconfigured to shear the inner lining of the vein (primarily but notlimited to the endothelial cell layer) when the helical coil is movedaxially along the vein in a deployed configuration.

Venous Disease

The device and method of the present disclosure may be employed to treator prevent venous disease. A combination of vein valve failure and veinwall weakness leads to the reflux of blood with subsequent complicationsof blood pooling in the lower limbs. The goal of superficial venousreflux treatment is to remove or occlude the refluxing vein allowingblood to divert to healthy veins and circulate effectively back to theheart. The Great Saphenous Vein (GSV) is the longest vein in the bodyand the most commonly treated vein for venous reflux disease. It'spathway runs from the foot to the groin where it has a junction with thedeep femoral vein. The GSV is most commonly the cause of venous reflux.Other veins include the Small Saphenous Vein (SSV), Anterior AccessorySaphenous Vein (AASV) and numerous tributary veins which can also betargets of treatment.

The venous network of the lower limbs is divided into threecomponents: 1) superficial veins located in the superficial compartmentsuperficial to the muscular fascia, draining the skin and subcutaneoustissue 2) deep veins that lie deep to the muscular fascia and drain themuscles of the lower limb, and 3) the perforating veins that penetratethe muscular fascia and connect the superficial and deep veins.

Understanding the fascial layers and compartments of the leg that theseveins are located in is important in understanding the risks involved incurrent treatment approaches. The GSV typically follows a course closeto the skin at a depth of 2 to 5 cms in persons of normal body habitus.It is bounded from the lower leg to the groin in an enclosed fascialspace by the muscular fascia below it and the saphenous fascia above.The latter being a portion of the membranous layer of the subcutaneoustissue. The two fascial layers, with the saphenous fascia above andmuscular fascia below, merge at each end to form a closed space, whichis called the saphenous compartment. The saphenous compartment containsthe saphenous vein and the accompanying arteries and nerves. Thesaphenous nerve is usually far from the great saphenous vein (GSV) andnot in the saphenous fascia above the knee. However, the saphenous nervelies in close proximity to GSV and is located within the saphenousfascia below the knee. The only truncal vein located in the saphenouscompartment is the GSV or its duplicate. All of the tributary veins andaccessory veins are located in the subcutaneous compartment, external tothe saphenous fascia and the saphenous compartment.

Segmental hypoplasia of the GSV occurs in 25% of patients withsuperficial venous disease [13]. This hypoplastic segment in the thighis often bridged by an accessory vein which runs outside the saphenouscompartment closer to the skin. If this or any other part of the GSVruns in very close proximity to the skin it may be difficult to create aplane of tumescence anaesthesia around the vein to protect the skin inpreparation for thermal venous disease treatment. In some instances onlynon-thermal methods or stripping of the vein can be performed. Tributaryveins in the thigh run outside the saphenous compartment and may becomevaricose in appearance if reflux develops. These are also less amenableto thermal treatment due to their more superficial position. The primarytwo tributary veins in the thigh are the anterior and posterior thighcircumflex veins. The Anterior Accessory saphenous vein in the thighruns within the saphenous compartment in parallel to the GSV but is notconsistent, present in approximately 14% of patients with varicoseveins. The small saphenous vein (SSV) begins at the lateral malleolusand drains into the deep vein in the popliteal space behind the knee. Itis close to the sural nerve which is vulnerable to injury using thermalmethods [14]. The fascial relationships of the SSV are more consistentthan the GSV.

Perforating veins connect the superficial veins with the deep veins byperforating the muscular fascia. There are up to 150 perforating veinsin the lower extremity with variable size and distribution. The medialcalf perforators are the most clinically significant and can lead tohigh velocity blood flow into the superficial system and venoushypertension. They are difficult to treat with surgical, thermal, glueand/or sclerosant methods due to their short length and close proximityto the deep venous system. Inadvertent propagation of heat, glue orchemical sclerosant directly into the deep venous system can lead to DVTand subsequent PE, a potentially fatal complication. Open surgicalligation is technically difficult and leads to significant morbidityfrom the incision. The junction of the GSV and SSV with the deep femoralveins, in the groin and posterior knee respectively, are also junctionalpoints between the superficial and deep systems and treatment of theincompetent superficial vein close to these regions carries a risk ofthromboembolic complications.

In view of these anatomical considerations, the use of thermal energy islimited due to the inherent risk of injury to adjacent skin and nerves.Furthermore, forward propagation of heat energy into non-target tissuesin the deep venous system is a potential cause of DVT and subsequent PE.Current non-thermal methods are also limited by the risk of damagingadjacent non-target tissues. Cyanoacrylate glue can be inadvertentlyplaced in the deep venous system without the ability to retrieve orrecapture it. Chemical sclerosants by their nature are effectivelycirculated into the deep venous system as they flow from the targetsite. Foam sclerosant preparations can propagate in clumped emulsions ofsclerosant and air traveling into the deep venous system potentiallydamaging the endothelium and leading to DVT. Chemical sclerosants canalso be inadvertently injected into subcutaneous tissue, nerves orarteries causing significant skin necrosis.

To counteract these limitations, an effective non-thermal device shouldhave the ability to be accurately and precisely deployed using standardultrasound techniques. It should also be possible to retrieve andrecapture the device if mal-positioned prior to treatment. No currentlymarketed device has this dual capability.

A mechanical ablation device, with the ability to be accurately deployedat a target site without the risk of uncontrolled forward propagation ordamage to surrounding tissues is preferable for the treatment of lowerlimb venous reflux. The ability to recapture and reposition furtherreduces the risk of user related error.

The method provided of vein occlusion without the use of a permanentimplant or toxic agent is preferable as it avoids the risk of infection,immune mediated inflammatory response, neurological side effects, debrismigration secondary to implant mechanical fatigue and patient discomfortdue to mass effect.

Bioabsorbable implant techniques have also previously failed to providelong term venous occlusion with recanalisation occurring followingabsorption [15].

Surprisingly, the authors have discovered that by using a purelymechanical non implantable solution, the natural thrombotic occlusionacts like an “implant” and is converted by the bodies natural healingmechanisms into a permanent occlusion in a process known as fibrotictransformation of thrombus.

Further to the method of occluding the GSV, SSV, AASV or largesuperficial tributary veins there is provided a method for treatingsmaller length incompetent tribuatry veins which commonly exist belowthe knee. These are currently treated with a procedure known asphlebectomy. This involves making a stab skin incision under localanaesthetic and using a vein hook device to manually extract the shortvein segment. This procedure is often performed on multiple veinsegments in the leg. It can be painful and uncomfortable for patientsdue to the requirement for multiple needlestick injections of localanaesthetic and the difficulty in fully anaesthetising each veinsegment. Often due to unacceptable patient discomfort or physicianpreference, chemical sclerosant is used instead. The increased number ofinjections of chemical sclerosant can increase the risk of systemictoxic side effects and local complications including skin necrosis frominadvertent injection of sclerosant into the subcutaneous tissue orarterial system.

In one embodiment the method of treating small tributary veins isperformed with a miniaturised helical coil as illustrated in FIGS.66A-66B and 67. The mechanism of action provided by this embodiment isthe same as previously described for the treatment of large veins suchas the GSV. Following insertion into the target vein, a miniaturisedcoil with abrasive outer surface is deployed exerting a radial force onthe vein wall. This surface denudes the inner layer upon withdrawal.

Referring to FIG. 65 in one embodiment the helical coil is loaded aroundthe needle as part of an intravenous cannula. Modifying the currentarrangement of an intravenous 14G cannula to decrease the size of theneedle used for entering the vein while maintaining the outer diameterof the sheath at 2.1 mm allows accommodation of the helical coil asillustrated in FIG. 65. Creating a more tapered tip with thepolyurethane outer catheter would allow skin access. Using currentintravenous access techniques of vein access, needle withdrawal andcannulae advancement as shown in FIG. 67. The miniaturised coil sectioncould be deployed by partial withdrawal of the outer polyurethanecannulae (FIGS. 66A and 66B). When the end of the treatment zone isreached the outer cannula can be used for recapture and atraumaticremoval of the coil. This proposed technique reduces the need for localanaesthesia as stab skin incisions are not required nor is any tractionon the vein required to pull out the vein as in hook phlebectomyprocedures. There is also no requirement for chemical sclerosantreducing the associated risks of skin necrosis.

Referring to FIGS. 68A-68D in another embodiment the vein is accessedwith a small gauge needle and a guidewire is passed into the vein. Anouter sheath similar to an introducer sheath, is passed over theguidewire as illustrated in FIGS. 69A-69B. This outer sheath ismanufactured to contain the coil adherent to its inner lining just belowthe aperture at the tip.

This allows the guidewire to pass through and past the coil within theintroducer. The coil is then deployed by partial withdrawal of the outersheath FIGS. 68A-68D. In another embodiment the coil is deployed byusing a peel-away introducer sheath as shown in FIGS. 70A and 70B. Inone embodiment, the coil can be reloaded into the sheath and used onseparate veins.

There follows a description of some indications associated with bodylumen that may be treated with the device and methods of the presentdisclosure:

Pelvic Vein Reflux

Abnormal reflux of blood in pelvic veins has been shown to be animportant but often previously unrecognised cause of recurrent varicoseveins in the leg, vulval/vaginal varicose veins and a condition known asPelvic Congestion Syndrome (PCS). It is also thought to be linked tohaemorrhoids. Reflux in the internal iliac veins and ovarian veins infemales are usually responsible for the development of these conditions.

PCS is characterized by visible congestion of the pelvic veins onvenography in women with a history of chronic pelvic pain for more thansix months. Most commonly the left ovarian vein is the cause of refluxand pelvic varicosities. Morbidity associated with PCS can be severeleading to a significant reduction in quality of life and patientdiscomfort. PCS manifests with different intra-pelvic symptoms includingnon-cyclical pain, urinary frequency and dyspareunia. Current treatmentis generally performed using catheter access via the jugular or femoralvein, following which the ovarian veins and/or the internal iliac veinsare occluded using metal embolization coils, chemical sclerosants suchas 3% sodium tetradecyl sulfate (STS), or a combination of both.Disadvantages of coil embolization include the high cost of treatmentrelated to coil devices and the risk of complications including coilmigration and vein rupture. Coil migration occurs when coils travelinadvertently to non-target sites such as the renal vein or via theinferior vena cava to the pulmonary veins causing pulmonary embolism.Coil migration has been reported to occur in up to 4% of cases and canlead to significant morbidity [16]. Some patients report persistentpelvic discomfort or flu like symptoms which is of unknown cause butcould be related to the coil implants. The use of endothermal laser orradiofrequency vein ablation has not been adopted for the treatment ofpelvic venous insufficiency. This is primarily due to the risk ofthermal damage to important surrounding pelvic structures adjacent tothe vessel wall. While transmural vessel perforation and damage tosurrounding tissues is rare with endothermal techniques, theconsequences during treatment within the pelvis are far greater than inthe lower limb. Furthermore, large volumes of tumescent anaesthesia areinjected around lower limb veins during treatment to shield surroundingtissues and prevent thermal injury and pain. This is obviously notpossible within the pelvis. Accordingly, a safe and cost-effectivedevice is still required for the treatment of pelvic vein reflux byocclusion. An optimal solution would be provided by a non-implantable,non-thermal method to reduce these risks.

In one aspect, the method of the present disclosure may be employed forthe treatment of pelvic vein reflux in which a helical coil device isused to mechanically denude the internal iliac and or ovarian veins tocause permanent occlusion. This occlusion will prevent venous reflux tothe leg veins which causes recurrent varicose veins, the venousterritories supplying the vagina/vulva and venous territories involvedin PCS. In another embodiment the denudation procedure can be combinedwith temporary balloon occlusion to reduce blood flow and promoteadherence of thrombus to the treated section of vein. This could beespecially beneficial in pelvic veins with higher volume reflux andvelocity. In one embodiment the procedure could be enhanced by thecombined use of chemical sclerosant and/or embolisation particles. FIG.71 is a schematic showing the venous anatomy relating to the pelvic veinreflux and the use of a helical coil to denude the internal iliac veinsand prevent refluxing flow to the venous territories involved thuscuring symptoms.

Deep Vein Reflux

Deep vein reflux caused by incompetent venous valves involving thefemoral vein in the lower limb cannot be treated by ablation andocclusion as it is vital for circulatory return of blood from the limbto the heart. Some incompetent venous valves have been obliterated byDVT but other are maintain normal valve leaflets but due to wall laxitythey no longer opppose correctly to prevent reflux. Current methods oftreatment involve invasive surgical procedures to create neovalves.Accordingly, there is a need for a less invasive procedure to restorevenous valve function. In one aspect, the method of the presentdisclosure may be employed for the treatment of deep vein reflux inwhich the helical coil device is deployed and withdrawn across anexisting valve. The outer surface is mildly abrasive to reduce the riskof thrombotic occlusion while maintaining the ability to disrupt theendothelial layer. This causes hypertrophy of the valve leaflets andsurrounding tissue with the effect of bringing the valve leaflets closertogether and restoring the one-way valve function to prevent reflux.

Haemorrhoids

As mentioned previously haemorrhoids can be treated with pelvic veinembolisation. Newer techniques also target the specific occlusion of thesuperior rectal artery to prevent filling of the dilated venous plexuscausing the internal haemorrhoids [17]. This artery is between 3 and 5mm in diameter in most instances. To avoid the placement of a permanentimplant and offer a more cost-effective solution for this commoncondition, improved treatments are required. In one aspect the method ofthe present disclosure is for treating hemorrhoids in which a helicalcoil device is used to mechanically denude the superior rectal artery tocause permanent occlusion and prevent filling of the venous plexus thuscuring the condition.

Varicocele

A varicocele is an abnormal dilation of veins surrounding the testes inmen. Clinically significant varicoceles are present in up to 15% ofadult men leading to pain, discomfort and reduced fertility. Treatmentis recommended in young men with testicular atrophy or reducedfertility. Current treatment involves occluding the testicular veinwhich supplies the abnormal dilated veins around the testes. Currentmethods of occlusion include permanent coil embolisation, glue, chemicalsclerosant or a combination of techniques. Accordingly, a less invasive,more cost-effective method is still required for the occlusion thetesticular vein which supplies the dilated veins in a varicocele. In oneaspect, the method of the present disclosure may be employed for thetreatment of varicoceles in which a single use helical coil is used tomechanically denude the testicular vein to cause permanent occlusion.FIG. 55 is a schematic showing the venous anatomy and the relatedprocedure to cause permanent vein occlusion.

Portal Vein Occlusion

Preoperative portal vein embolisation (PVE) is an elective procedure toterminate portal blood flow to a selected portion of the liver prior tomajor liver resection. PVE, initiates hypertrophy of the liver tissuethat is to remain following the planned major resection and may allow amore aggressive resection. It is used as an adjunctive step in thetreatment of primary and secondary liver metastases from colorectalcancer. Current techniques involve access to the portal venous systemusing direct image guided transhepatic access with subsequent injectionof embolisation agents including glue, polyvinyl alcohol (PVA) andmetallic spheres or coils. Many of these techniques are costly and thepatient may be inoperable during the course leading up to the plannedresection. Accordingly, a more cost-effective approach is required. Dueto the pro-coagulative state of most patients undergoing portal veinprocedures as an adjunct to tumour resection, a non-implant methodrelying on thrombotic occlusion of selected portal veins could beeffective. In one aspect, the method of the present disclosure may beemployed for the preoperative occlusion of portal veins is proposed inwhich a helical coil device is used to mechanically denude the portalveins to cause occlusion. This occlusion will promote hypertrophy of theremaining liver segments and improve the likelihood of patient survivalpost planned resection. FIG. 53A is a schematic representation of portalvein occlusion using a non-implant mechanical denudation method.

Vein Grafts

Coronary artery bypass graft (CABG) surgery is the standard of care forpatients with left main coronary artery disease (CAD) and three-vesselCAD. Peripheral artery bypass grafting (PABG) surgery is performed inpatients with late-stage peripheral artery occlusive disease. Theinternal mammary artery is commonly used for revascularization incoronary bypass surgery, however, veins (almost exclusively the greatsaphenous vein) remain the most commonly used grafts, especially forPABG surgery. The interposition of vein grafts into the arterial systemexposes the vein to higher stretch forces and shear stress which mayresult in excessive inflammatory changes within the venous wall known asintimal hyperplasia leading to occlusion and vein graft failure. Thepatency rate at 10 years following vein graft surgery is only 60% [18].It is not well understood why some vein grafts remain patent whileothers become occluded in the long term. All veins undergo someremodelling or “arterialisation” when transferred to the arterialsystem. However, an excessive and persistent inflammatory responsecauses graft failure in the long term. New research indicates that thecondition of the vein prior to grafting may be an important predictor ofgraft failure. Veins with already hypertrophic, synthetic predisposedsmooth muscle cells in the media layer have a worse prognosis.Accordingly, a way to increase the long-term success rates of veingrafts for arterial disease is an important clinical need and may beachieved by preconditioning or modifying the vein graft prior to use asa conduit in the arterial system. In one aspect of the presentdisclosure a method for the pre-treatment of veins to be used as graftsin the arterial system for the treatment of CAD and PAD is proposed. Ahelical coil with a less abrasive surface or partially abrasive surfaceis provided to cause vein wall thickening without complete thromboticocclusion and subsequent fibrosis. The depth of vein wall disruptionmust be specific to develop the correct inflammatory response which doesnot predispose the vein to graft failure. This adjunctive procedure isperformed ideally 4 to 12 weeks prior to graft implantation to allow thecellular changes involved in vein remodelling to occur and subside. Thismay improve the ability of the vein to adapt to the arterial environmentof greater pressure and higher shear forces because the inflammatorychanges have already taken place and stopped following a once-offmechanical disruption by the treatment. The uncontrolled excessiveinflammatory and hypertrophic changes will then be less likely to occurwhen placed into the arterial system. This could prevent excessiveuncontrolled media hypertrophy and intimal hyperplasia occurring andreduce the risk of mural atheroma formation which is a major cause ofcardiac graft failure. FIGS. 72A-720 show the histological differencesbetween a normal vein, an arterialised vein and a failed vein graft.

Aterio-Venous (AV) Fistula

AV Fistulae are surgically created anastomosis between the arterial andvenous circulation to enable the treatment of end stage kidney disease(ESKD) with dialysis. Patients with a working AVE have lower morbidityand mortality rates, and lower treatment costs compared to patients whorely on central venous catheters for dialysis. There is an unacceptablehigh rate of primary failure with AVF creation ranging from 20 to 60%.The failure rate had risen in recent years due to the ageing populationdependent on AVE for dialysis and the higher pump speeds used indialysis [19].

The main cause of failure is stenosis at the venous segment of theanastomosis. The underlying mechanisms involved in AVF creation arepoorly understood but insufficient outward remodelling and excessiveintimal hyperplasia are thought to be involved. Accordingly, an improvedway of forming an AVE for use in ESKD patients is urgently needed. Inone aspect of the present disclosure a helical coil with reducedabrasiveness or partially abrasive is used prior to the surgery forcreation of the anastomosis to produce a vein with a healthy pattern ofremodelling. This procedure should ideally be performed 4 to 12 weeks inadvance of AVE creation to allow cellular changes to occur and subside.This preconditioning of the vein could reduce the inflammatory responseand uncontrolled remodelling which leads to AVE primary failure when anormal vein is acutely exposed to arterial pressures and flow rates.This could increase the success rate of AVE procedures. This techniquemay also prevent AVF Steal syndrome whereby the venous side of theanastomosis becomes overly enlarged and leads to ischaemia in theterritories supplied by the arterial side.

Thrombectomy

Thrombotic occlusions can occur anywhere in the arterial or venoussystem and are typically composed of red blood cells, activated clottingfactors, platelets and inflammatory cells. Over time from minutes todays the thrombotic mass becomes organised and adherent to the vesselwall especially if there is vessel wall damage. Previously describedembodiments of the present disclosure were designed to promote thisevent when vessel occlusion is required, primarily in the setting of thesuperficial venous reflux.

The authors have also discovered that a radially expansive helical coilcan also be used to remove adherent thrombus to the vessel wall if theabrasive surface is modified to be only present on the leading edge andinner surface of the coil while the outer surface remains smooth toprevent vein wall trauma.

Acute deep vein thrombosis (DVT) is a potentially life-threateningcondition if embolisation to the lungs occurs known as pulmonaryembolism (PE). Significantly large DVTs remaining in the peripheralveins can also lead to significant morbidity from chronic venoushypertension in the lower limb. Anticoagulation is the cornerstone oftreatment to help dissolve clots and prevent embolisation. New methodsto treat patients in the acute setting by removal of the clot usingmechanical, chemical lysis or ultrasound techniques have emerged in thepast 10 years and shown to improve outcomes in certain patient groups.Removing clot which has become adherent to the vein wall is technicallydifficult and failure can lead to poorer outcomes. Some newertechnologies which use complex mechanical systems, aspiration orultrasound are not reimbursed due to their high cost. A fogarty balloonis a low-cost alternative to thrombus removal but is ineffective foradherent thrombi.

In the arterial system a similar need exists for the removal of anorganised thrombus causing acute limb ischaemia. In the neurovascularsystem stent recapture systems are used to retrieve thrombus and preventstroke. In both these settings more organised, adherent thrombusrepresents a technical challenge. There is therefore a need to developimproved solutions for removal of adherent clot or thrombus on vesselwalls. In one embodiment a method is provided for using a helical coilwith abrasive inner and leading-edge surfaces to dislodge thrombus fromthe vessel wall without causing endothelial trauma. FIG. 73 shows howsuch a device can remove thrombus while leaving the endothelial surfaceintact and less likely to re-thrombose.

The device is deployed distal to the thrombotic occlusion and withdrawnproximally towards the access site. Following dislodgement of thethrombus a fogarty balloon, recapturing basket or aspiration cathetercan be used to remove the thrombus from the circulation. This willrestore blood flow and prevent the sequelae of vessel occlusionoccuring.

In-Stent Occlusion

Percutaneous stenting of the vasculature is commonly performed toreinstate blood flow in partially stenosed or occluded arterial orvenous circulation. In-stent thrombosis is a relatively uncommon butpotentially life threatening complication occurring after approximately1% of cardiac stent procedures. Stents placed in diseased arteries mayhave struts overlying calcified or atheromatous plaques. Elevated stentsstruts in these situations can lead to a failure of coverage by theneointima especially in drug eluting stents [20]. This typicallymanifests as late or very late onset stent thrombosis over 1 yearfollowing implantation. There is a need to reduce the rate of in-stentthrombosis following such procedures. In one aspect of the presentdisclosure a helical coil with an outer abrasive surface that coverspart of the coil circumference is provided. This allows selectivetreatment of a section of arterial surface which is likely to remainuncovered following statement. FIGS. 74A and 74B illustrate the methodof using a partial abrasive coil to selectively pre-treat a section ofartery prior to stent placement. This increases the likelihood of stentstrut coverage by the neointima and reduces the risk of late stentrestenosis. Imaging technologies such as intravascular ultrasound (IVUS)can be used to orientate the device and allow the operator toselectively target a desired section of vessel wall.

Arterial Occlusion

Selective occlusion of arteries and in general the arterial supply tospecific tissues is an effective treatment for a variety of diseasestates. Tumour embolisation is a technique in which arteries supplyingeither benign or malignant tumours are occluded using a variety ofmethods via a percutaneous approach including synthetic or bioabsorbablebeads, metallic spheres, glue or metallic coils. Common complicationswith the use of these agents include migration to non-target vessels,excessive occlusion causing necrosis of normal tissues, pain, infectionrelated to combination of foreign body with necrotic tissue [21].Accordingly, there is a need for a less invasive, non-implantabletreatment with lower complication rates for the embolisation of arteriessupplying benign or malignant tumours.

Referring to FIGS. 52A and 52B, these is illustrated a tumour 240 and anarterial blood supply to the tumour comprising small arteries 241. Thedevice of the present disclosure may be employed to occlude one of thesmall arteries and starve the tumor of blood supply. FIG. 52B shows thevein denuding head 242 of a device of the present disclosure showndeployed in a small artery, where the helical coil circumferentiallyengages a lumen of the artery. Referring to FIG. 52A, the device isadvanced along the artery feeding the tumor, and deployed at the point243, and then retracted proximally. The retraction of the helical coilalong the artery, coupled with the circumferential contact between theroughened surface of the helical coil and the lumen of the artery,causes a section of the lumen of the artery to be denuded with removalof the epithelial layer of cells, and consequent thrombus formation atpoint 243 resulting in occlusion of the artery.

Uterine Fibroids

Uterine fibroids are benign lesions which can cause significant pelvicpain and dysmenorrhea. They can be treated by hysterectomy or withminimally invasive embolisation of the uterine arteries supplying thefibroid. The most commonly used embolic agents for uterine arteryembolisation (UAE) are polyvinyl alcohol (PVA), tris-acryl gelatinmicrospheres, and polyzene-F hydrogel microspheres. Complicationsinclude migration of embolic material to non-target tissues, excessivenecrosis causing pain and infection. Accordingly, there is a need for aless invasive, non-implantable treatment with lower complication ratesfor the treatment of uterine fibroids. In one embodiment a method isprovided for the use of a helical coil with abrasive outer surface tocause partial or full occlusion of the uterine artery or distal branchessupplying a uterine fibroid. Reducing or eliminating blood flowdecreases the size and relieves symptoms caused by the fibroid. Causingsufficient stenosis of the vessel using this method by inducing intimalhyperplasia may reduce the risk of necrotic complications whilepreserving the size reduction effect on the fibroid. This method couldalso be used to treat the following conditions which include but are notlimited to; arteriovenous malformations (AVMs) in the pulmonary,cerebral or hepatic circulation, malignant tumours, benign prostatichypertrophy (by prostatic artery occlusion).

Patent Foramen Ovale

Patent foramen ovale (PFO) is a common cardiac wall abnormality found inapproximately 30% of the adult population. While usually a benignfinding in some the PFO can open enabling a paradoxical embolus totravel from the venous to arterial circulation potentially causingstroke and systemic embolisation. The treatment in individuals with ahistory of cryptogenic stroke is percutaneous closure using septaloccluders. These devices are permanent implants deployed across thedefect. The anatomy of a PFO involves the overlapping of the primum andsecundum atrial septa which form a flap valve that can open when theright atrial pressure exceeds the left atrial pressure such as incoughing or sneezing. These devices are expensive and can causecomplication including thrombosis and stroke. There is a need for a lessinvasive treatment with lower risk of complications. In one embodiment amethod is provided for the use of a coil or hooped shaped abrasivedevice to denude the contacting surface of the atrial septal flapsinvolved. This leads to an inflammatory response which cause adhesionformation between the flap surfaces leading to permanent closure of thePFO and elimination of stroke risk. A similar method could be usedwithin the heart to create scar tissue and thickening to block nerveconduction at points of aberrant conduction which cause arrhythmias.

Patent Ductus Arteriosus

The ductus arteriosus (DA) is a fetal vascular connection between themain pulmonary artery and the aorta that diverts blood away from thepulmonary bed. After birth, the DA undergoes active constriction andeventual obliteration. A patent ductus arteriosus (PDA) occurs when theDA fails to completely close postnatally. Histologically, ductal tissuediffers from that of the adjacent aorta and pulmonary artery. The intimaof the ductus is thicker, and the media contains more smooth musclefibers arranged in a characteristic spiral fashion. The DA may take avariety of shapes and forms. Small PDAs are typically <3 mm in diameter.The optimal treatment method for infants with a PDA necessitatingclosure remains a subject of controversy and debate. Currentpercutaneous treatment options include coils and occlusion devices.Limitations of these treatments include the high cost and risk of coilmigration causing embolic complications. Occlusion devices can lead toserious complications such as coarctation of the aorta as the childgrows if not sized correctly [22]. Accordingly, there is a need for lessinvasive effective percutaneous treatments for PDA. In one embodiment ahelical coil with an outer abrasive surface is used to denude the DAcausing thrombosis and fibrotic occlusion over time. This would relievesymptoms associated with shunting and reduce the risk of endocarditis byclosing the DA. This technique could also be used to treat smalldiameter atrial septal defects in a similar manner.

Aortic Aneurysms

Abdominal aortic aneurysms (AAAs) are abnormal dilatations of the aortawhich can be complicated by rupture causing significant morbidity andmortality. Treatment for large aneurysms is aimed at reducing the riskof rupture. Treatment options are either open surgery with graftplacement or endovascular aneurysm repair using large covered stentgrafts (EVAR). EVAR is a less invasive procedure with significantlyfaster recovery time and lower risk of renal injury. However, the longterm outcomes of EVAR are limited by endoleaks in up to 20% of patients,requiring radiological monitoring, revision surgery or adjunctiveprocedures [23]. Endoleaks can be classified as Type I to Type V. Type Iendoleaks occur at the proximal or distal graft attachment sites. Bloodenters through gaps between the vessel wall and the graft and fills thesac leading to a risk of rupture. Type II endoleaks occur whenretrograde flow occurs into the aneurysmal sac via side branches fromlumbar or mesenteric vessels and also leads to a risk of rupture. Type Iand II endoleaks account for the majority of morbidity associated withthe EVAR post-operative course. Current treatment methods for Type Iendoleaks include miniature screws and additional stent graftplacements. Type II endoleaks can be treated with embolisation coilplacement in the lumbar or mesenteric vessels supplying the sac. All ofthese methods are invasive, costly and carry complications of aorticwall rupture and infection. Accordingly, there is a need for techniquesto reduce the risk of Type I and Type II endoleaks. In one embodiment amethod is provided for preparing sections of the aorta close to graftattachment sites to reduce the risk of Type I endoleaks. This isperformed by using a helical coil to denude the endothelial lining inthese specific locations whose locations can be easily determined basedon preoperative imaging planning. By performing this procedure, thearterial wall is primed to develop a neointimal proliferation at thegraft attachment site and reduce the risk of blood leakage and Type Iendoleaks. This benefit will reduce the risk of adjunctive procedureswhich can complicate the post-operative course. A similar method couldbe used to treat Type I endoleaks as they occur by inserting anexpandable resilient abrasive device in the gap where the endoleak isoccurring to cause thrombotic occlusion with fibrotic transformationover time. A further method is provided for the treatment of Type IIendoleaks by using an expansive resilient abrasive element to denude thefeeding lumbar or mesenteric arteries causing occlusion and preventingthe risk of sac rupture. As the flow in these arteries is retrogradefrom anastomotic connections, they are more likely to behave like veinsand be amenable to thrombotic occlusion with the permanent implantationof coils. A similar method could be used to treat paravalvular leaksassociated with percutaneous heart valve replacement. Paravalvular leakspost percutaneous mitral and aortic valve replacement procedures leadsto postoperative morbidity and in some cases revision surgery.

Diabetes Intervention Treatment

Duodenal Mucosal resurfacing (DMR) is a new technique that has beenshown to improve blood glucose control in diabetic patients in earlyclinical studies [24]. The duodenum is an important conduit for glucoseabsorption and signalling to endocrine organs. It is thought that theduodenal mucosa becomes hyperplastic in response to chronic high sugardiets which creates an insulin-resistant signal, worsening glucosecontrol. By ablating this hyperplastic mucosa, a new mucosal surface canregenerate without harmful signalling.

The anatomy of the duodenum shares some important characteristics withthe venous system. It has a tortuous curved pathway, it is highlycompliant and distensible and muscular wall contractions can causeconstriction. The aim of treatment is to safely ablate only thesuperficial mucosal layer without affecting the deeper muscularis layerbelow. This is performed over the length of the duodenum ofapproximately 10 cms.

Current methods in development involve placing an expandable ballooncapable of transmitting hydrothermal energy from fluid within theballoon to the duodenal wall and thus causing ablation or damage to thecells on the mucosal lining [22]. This method requires a skilledendoscopist to create a thermal barrier by lifting the mucosa away fromthe submucosa. This is currently achieved by suction channels around thecircumference of the balloon to hold the superficial mucosa layer whilea needle is inserted submucosally to inject saline. There is a risk ofduodenal wall perforation and damage to deeper muscularis layer if thisis not performed correctly. Accordingly, there is a need for a lessinvasive, easier to perform, lower cost and faster treatment which canselectively ablate the superficial layers of the duodenum to a depth ofno greater than 0.6 mm. In one embodiment of the present disclosure aradially expansive resiliently deformable abrasive device is deliveredvia a channel in a standard endoscope as illustrated in FIG. 75. Theabrasive element is deployed to contact the duodenal wall distally nearthe junction with the jejunum. The abrasive element has a surfaceroughness with maximum peak to trough distance of 0.6 mm. The device iswithdrawn proximally towards the stomach. During withdrawal it causes acircumferential denudation or damage to the mucosal layer. This allowsregeneration and improvement of glucose control. A similar method couldbe employed in other parts of the gastrointestinal tract to treatpathologies affected by the absorption of lipids, iron, vitamins andminerals including manganese.

Small Intestinal Bacterial Overgrowth

Small intestinal bacterial overgrowth (SIBO) occurs when the small bowelis colonised by excessive microbes that are normally present in thecolon. Invasive bacterial strains injure the intestinal surface by theproduction of enterotoxins and through direct wall adherence.Fermentation of unabsorbed carbohydrates results in bloating,distension, and flatulence. Inflammation or the ileum can also occurcausing diarrhoea and malabsorption of nutrients. The small bowel(jejunum and duodenum) normally has significantly lower concentrationsof bacteria and other micro-organisms compared to the colon. Theboundary between these sections of the gastrointestinal tract iscontrolled by the ileocaecal valve. When this valve becomes incompetentit can allow the reflux of large bowel contents into the small bowel.This encourages bacterial overgrowth which feeds off the nutrient richcontents of the small intestine [25]. Antibiotic treatment to stopbacterial overgrowth in the small bowel is currently used in primarytreatment. However, approximately 40 percent of patients with smallintestinal bacterial overgrowth (SIBO) have persistent symptoms afterinitial antibiotic treatment. It has been demonstrated that abnormalreflux through the ileocaecal valve is a causative factor in SIBO [25].Accordingly, there is a need for more effective treatments for SIBO. Inone embodiment a radially expandible abrasive device is used to disruptthe mucosal layers of the ileocaecal valve and ileum. This causes aninflammatory response followed by hyperplasia which could reduce thediameter of the ileocecal valve making it less likely to allow reflux offluid from the colon. A secondary effect could be to ablate the areas ofthe ileum colonised by adherent bacteria to allow regeneration of normalor non-colonised mucosa. This method could be used in conjunction withantibiotic therapy to enhance the effect and lower the high recurrencerates. A similar method could be used to tighten the gastro-oesphagealjunction which can be the cause of gastric reflux in the presence ofsphincter laxity.

Barrett's Oesphagus

Barrett's esophagus (BE) is a premalignant condition for oesphagealcarcinoma whereby cell changes in the lower oesphagus occur due tochronic injury and inflammation due to gastro-oesphageal reflux disease(GORD). It is estimated to be present in 10% of GORD patients. Earlyintervention can prevent progression to cancer. Current earlyintervention methods include thermal and radiofrequency ablation of thesuperficial layers affected to allow regeneration with normal tissue[26]. Radiofrequency ablation is a currently used technique involvingendoscopic insertion of a radiofrequency probe. The main disadvantage ofthis method is the high cost of the radiofrequency device. Accordingly,there is a need for simpler, cost effective treatments for this commoncondition. In one embodiment a method is provided for the endoscopicdeployment of radially expansive abrasive element to mechanically ablatethe abnormal cells in the lower oesphagus thus reducing the risk ofcancer development. Given that the histological grading and definitivediagnosis of Barrett's oesphagus is highly challenging for pathologists,a further advantage of this method is that it allows collection of cellson the denuding head which can be analysed post procedure. This is incontrast to thermal methods which completely destroy cells. Thisfunction of cell collection could also be applied to the diagnosis andmanagement of premalignant or malignant lesions in other parts of thegastrointestinal tract such as the colon, pulmonary bronchi andbronchioli, uterus, cervix, urinary tract and bladder.

Peri-Anal Fistulae Management

Perianal fistulae are abnormal connections between the rectum and theskin surrounding the anal canal. They are a present in patients withinflammatory bowel disease and lead to significant morbidity due toinfection, pain and bleeding. They are difficult to treat with currentmethods including invasive surgical resection or application of a setonstitch to gradually remove the channel over a long term treatmentcourse. These treatment options carry a high recurrence rate [27].Accordingly, there is a need to develop a less invasive more effectivetreatment for perianal fistuale. In one embodiment a radially expansiveabrasive device is provided for deployment and withdrawal in the fistualtract. This caused denudation of the tract which is lined withendothelial cells. The subsequent inflammatory reaction causes scarringand blockage of faecal contents from entering the tract and preventinghealing. Subsequent closure of the tract by a fibrotic inflammatoryreaction prevents symptoms. A similar method could be used to seal orclose sections of disease lung that occur in chronic obstructive lungdisease. When inhaled air enters these parts of the disease lung oxygenexchange does not occur leading to a reduction in blood oxygen levels.There is a need to occlude or seal bronchioli or alveoli in theseinstances to divert air to healthy lung tissue.

Sterilisation

Female sterilisation is commonly performed by fallopian tube ligationwhen permanent contraception is desired by the patient. Current methodsrange from open surgical ligation, salpingectomy and minimally invasiveclip placement. Complications of these procedures include pain, bleedingand infection. A less invasive reliable method which avoids surgicalresection or permanent implantation is required. In one embodiment aradial expansive helical device is inserted, deployed and withdrawn inthe fallopian tube. This disrupts the endothelial and subendotheliallayers initiating an inflammatory response causing fibrotic occlusion ofthe fallopian tube over time. This technique could also be applied tomale sterilisation procedures on the lumen of the vas deferens.

FIGS. 52A to 55 illustrate uses of the device of the present disclosureto occlude various vessel in the treatment of disease in a subject.

Referring to FIGS. 53A and 53B, the use of the device of the presentdisclosure to occlude the portal venous system is illustrated. Thistreatment may be employed to treat liver cancers, by occlusion of partsof the portal vein system which bring nutrients from the intestines 254to the liver. In the figures, a vessel denuding head 252 is shown in aportal vein 251 in a deployed configuration. The retraction of thehelical coil along the vein, coupled with the circumferential contactbetween the roughened surface of the helical coil and the lumen of thevein, causes a section of the lumen of the portal vein to be denudedwith removal of the epithelial layer of cells, and consequent thrombusformation resulting in occlusion of the vein.

Referring to FIG. 54, there is illustrated a use of the device of thepresent disclosure to treat arteriovenous malformation, which is anabnormal tangle of blood vessels 261 connecting the venous 262 andarterial 263 blood vessels. In the embodiment illustrated, a device ofthe present disclosure is advanced along an artery and into themalformation, and the helical coil 264 is deployed into circumferentialcontact with the vessel 261 and retracted to denude the lumen of thevessel, causing thrombus formation and occlusion of the vessel 261,thereby shutting the shunt between the arterial and venous blood system.

Referring to FIG. 55, there is illustrated a use of the device of thepresent disclosure to treat spermatic vein insufficiency (orvaricocele), which is a condition similar to varicose veins that occursin the veins in the scrotum 272 and which can cause infertility, painand discomfort for the patient. In the embodiment illustrated, a deviceof the present disclosure is advanced along a left internal spermaticvein 270, and the helical coil 271 is deployed into circumferentialcontact with the vein 270 and retracted to denude the lumen of thevessel, causing thrombus formation and occlusion of the vessel 270,thereby occluding the vein and treating the condition.

Referring to FIGS. 56A to 56C, the use of a device of the presentdisclosure, and in particular the ability of the device to self-adjustits diameter to adapt to vessels of varying diameter is illustrated. Thecoil is formed from nitinol, and in a relaxed state forms a helical coilhaving a diameter that is larger than the vessel to be treated. When thecoil is deployed in a vessel (generally deployed from a deliverycatheter), the catheter expands to conform to the circumference of thevessel, exerting an outward radial force against the circumference ofthe vessel through at least one turn of the coil. FIG. 56A shows thedeployed helical coil 280 in a vessel 281 in circumferential contactwith the lumen of the vessel approaching the narrowed section 282 of thevessel, with the diameter of the proximal part of the coilself-adjusting to the smaller diameter of the vessel. FIG. 56B shows thehelical coil 280 having passed through the narrowed section 282 andmaintaining circumferential contact with the lumen of the vessel justproximal of the narrowed section. FIG. 56C shows the helical coil movingproximally of the narrowed section and self-adjusting to maintaincircumferential contact with the lumen of the vessel as it widens.

Referring to FIGS. 57A to 57C, the use of a device of the presentdisclosure is illustrated, in particular how the helical coil formingpart of the device of the present disclosure can navigate through valvesin veins as it is pulled through a section of a vein: (A) the deployedhelical coil 290 attached to control arm 31 and in circumferentialcontact with the lumen of the vein 291 distal of the valve 292; (B) thehelical coil 290 being retracted proximallythough the valve 292 with thediameter of the coil self-adjusting to prevent the coil snagging on thevalve leaflets; and (C) the helical coil moving proximally of thenarrowed section and self-adjusting to maintain circumferential contactwith the lumen of the vessel proximal of the valve.

Referring to FIGS. 58A to 58B, the use of a device of the presentdisclosure is illustrated, in particular how the helical coil formingpart of the device of the present disclosure can self-adjust to navigatethrough a section of vasculature 300 that progressively narrows with thediameter of the helical coil 301 self-adjusting to maintaincircumferential engagement with the lumen of the vessel: (A) thedeployed helical coil 301 in circumferential contact with a wide section302 of the vessel; (B) the deployed helical coil 301 in circumferentialcontact with a narrower section 303 of the vessel;

Referring to FIGS. 59A to 59C, the use of a device of the presentdisclosure is illustrated, in particular how the helical coil formingpart of the device of the present disclosure can self-adapt to varyingvessel diameter and navigate a tortuous vessel: (A) the deployed helicalcoil 310 in circumferential contact with the lumen of the vessel at anarrowed section 311 of the vessel; (B) the helical coil 310 navigatingthrough a sharp turn 312 in the vessel while maintaining circumferentialcontact with the lumen of the vessel; and (C) the helical coil 310navigating through a second sharp turn 313 in the vessel of greaterdiameter while maintaining circumferential contact with the lumen of thevessel. It can be seen from the figures how the helical coil adapts tothe changing diameter of the vessel and maintains circumferentialcontact with the lumen of the vessel, even as it passes through tortuousturns.

Referring to FIGS. 60A, 60B, and 60C, the use of a device of the presentdisclosure is illustrated, in particular how the helical coil formingpart of the device of the present disclosure can self-adjust thediameter of the coil to maintain circumferential engagement with thelumen of the vessel when the vessel constricts due to a vasospasm: (A)the deployed helical coil in circumferential contact over length Iwithin a wide vessel of diameter D prior to vasospasm of the vessel; (B)Section A-A illustrates an axial view of the coil within the vesselunder a constraint pressure P which translates as a hoop force (HF)within the coil. This HF causes lengthening of the coil, promoted by itsopen ended design (C) the deployed helical coil in circumferentialcontact over an extended length L within constricted vessel of diameterd during a vasospasm of the vessel.

Referring to FIGS. 62A and 62B, the use of a device of the presentdisclosure to partially occlude a body lumen, and in the embodimentillustrated, to specifically treat vasculature having abnormally highblood volumes or high blood flow rates, to partially occlude the vesselto normalise the blood volume or flow. (A) shows a pulmonary artery 330prior to treatment, with the device of the present disclosure includinghelical coil 331, control arm 31 and catheter member 2 deployed in theartery and being pulled in the direction of the arrow marked X; (B)shows the pulmonary artery of 330 after treatment with the device of thepresent disclosure with intimal hyperplasia of 333 partially occludingthe artery to provide for reduced blood volume and flow through theartery.

Vessel Wall Evaluation

Understanding the biophysical properties of vessel walls in the arterialand venous system is important for both predicting disease progressionand assessing the response to treatment.

Abnormalities in the vascular endothelium are now seen as earlyprecursors of vascular disease [28]. One such marker is how well thevessel can contract or spasm in response to mechanical or chemicalstimuli. Chronic high blood pressure and/or chronically uncontrolledblood sugar levels cause damage to the endothelial layer and can bedetected at a much earlier stage than atherosclerosis, arterial stenosisor occlusion. Acetylcholine iontophoresis is a method of testing theendothelial response in conjunction with measuring blood flow across thesection of vessel. These methods have shown experimentally thatendothelial function is inhibited by consumption of sugar sweetenedbeverages and chronic high blood pressure states [29]. During vascularinterventional procedures there is currently no way to assessendothelial cell function in or adjacent to arthersclerotic lesions.Accordingly, there is a need to collect more information on the functionon the endothelium to inform treatment decisions and inform prognosis.During intravascular stent placement for instance there is currently noway for e physicians to know how the vessel wall is responding toexpansion during angioplasty. This can lead to complications includingvessel rupture, haemorrhage and thrombotic occlusion [30]. Currently theair pressure in the inflated balloon is measured and inflated tostandard levels based on experience and angiographic appearance postinflation. However, due to differences in vessel wall characteristicsand inter patient differences, occurrences of complications such asvessel wall rupture remain difficult to predict. In one embodiment aradial expandable element which contacts the vessel wall at discretedistant points is used to measure the response of the endothelium tochemical or mechanical stimuli. Mechanical stimuli can be provided bythe radial force of the device itself which can be static or modifiablevia a control arm. Chemical stimuli can be provided by coating ofpharmacological agents on the device surface. In one embodimentpiezoelectric sensors are incorporated into the radial expansive elementto measure pressure and flow effects on the coil during intraluminalprocedures. An expansive element within a vein lumen generating anoutward radial force will cause a hoop force (HF) within the vesselwall. This stretching HF will cause an opposing compressive hoop forcewithin the intra luminal device. Thus, measuring the intrinsiccompression within the device will act as a surrogate marker tocharacterise the response of the vessel wall to stretch. This data canbe recorded and stored in a central control unit. This data could beused for future performance enhancements including automation ofprocedures in the vascular system. This data could also be analysedeither manually or by utilising machine learning methods to determineprognosis and validate diagnostic markers of vascular disease.

Equivalents

The foregoing description details presently preferred embodiments of thepresent disclosure. Numerous modifications and variations in practicethereof are expected to occur to those skilled in the art uponconsideration of these descriptions. Those modifications and variationsare intended to be encompassed within the claims appended hereto.

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1-20. (Canceled)
 21. A vein denuding device comprising a coil configuredfor transluminal delivery to a vein to be treated during the procedureand deployment whereby the coil circumferentially engages an inner lumenof the vein, in which the coil has a roughened lumen-engaging surface,so that when it is deployed the roughened lumen-engaging surface bearsagainst the inner lumen of the vein, in which the roughenedlumen-engaging surface of the coil comprises a series of teeth, wherebyaxial movement of the coil along the vein mechanically denudes a lengthof the vein with consequent disruption of the endothelial and medialayers of the vein.
 22. A vein denuding device according to claim 21, inwhich each tooth extends transversely across the lumen-engaging surfaceof the coil.
 23. A vein denuding device according to claim 22, in whicheach tooth has a triangular profile.
 24. A vein denuding deviceaccording to claim 21, configured to mechanically denude the vein to adepth of 5 to 100 μm.
 25. A vein denuding device according to claim 21,in which the coil is oversized relative to the diameter of the veinbeing treated to ensure circumferential engagement between the roughenedsurface of the coil and lumen of the vein.
 26. A vein denuding deviceaccording to claim 21, in which the coil is resiliently deformable toallow the coil to reflexively self-adjust its diameter in response tovariable vessel diameters and variable axial forces during axialmovement along a treatment zone of the vein while maintaining an outwardradial force on the vein.
 27. A vein denuding device according to claim21, in which the coil is helical and has 1 to 3 turns.
 28. A veindenuding device according to claim 21, in which the coil is helical andis configured to have a pitch of about 0.5 to 1.5 times the coildiameter in the coiled configuration when deployed.
 29. A vein denudingdevice according to claim 21, in which the coil has a flat crosssection.
 30. A vein denuding device according to claim 21, in which adistal end of the coil comprises an atraumatic head.
 31. A vein denudingdevice according to claim 21, in which the coil comprises a shape memorymaterial and is configured to adopt a coiled configuration whendeployed.
 32. A vein denuding device according to claim 21, including anelongated catheter operatively attached to the coil, wherein the coil isadjustable from an uncoiled delivery configuration suitable fortransluminal delivery within the catheter member and a coiled deployedconfiguration having a diameter equal to or greater than the vein to bedenuded.
 33. A vein denuding device according to claim 21, in which thedevice comprises an elongated control arm for the coil disposed withinthe catheter member.
 34. A vein denuding device according to claim 21,in which a diameter of the coil varies along its length.
 35. A veindenuding device according to claim 21, in which a diameter of the coilincreases towards one end.
 36. A vein denuding device according to claim21, in which a diameter of the coil increases towards a proximal end.37. A vein denuding device according to claim 21, in which a diameter ofthe coil increases towards a mid-point along the coil, and thendecreases.
 38. A vein denuding device according to claim 21, in which adistal tip of the coil terminates at a point disposed along, or adjacentto, a longitudinal axis of the coil.
 39. A vein denuding deviceaccording to claim 21, in which the coil has a proximal section of afirst diameter, an intermediate section of reduced diameter relative tothe proximal section, and a distal section of increased diameterrelative to the intermediate section.
 40. A vein denuding deviceaccording to claim 21, in which the coil has a proximal and distalhelical coil section, and an intermediate connecting section that is nothelical and may be straight or curved.